Role of abnormal lipid metabolism in development, progression, diagnosis and therapy of pancreatic cancer

World Journal of Gastroenterology

Volumn 20, Issue 9, 2014, Pages 2279-2303

  Swierczynski, Julian ^a   Hebanowska, Areta ^a   Sledzinski, Tomasz ^a  

^a MEDICAL UNIVERSITY OF GDANSK   (Poland)

Author keywords

Cyclooxygenase 2; Farnesylation; Fatty acid synthase; Hypoxia inducible factor 1 ; Lipid metabolism; Lipogenic enzymes inhibitors; Monounsaturated fatty acids; Oncogenes; Pancreatic cancer; Tumor suppressors

Indexed keywords

ACETYL COENZYME A CARBOXYLASE; ACONITATE HYDRATASE; ACYL COENZYME A DESATURASE; ADENOSINE TRIPHOSPHATE CITRATE LYASE; ASPARTATE AMINOTRANSFERASE; BETA CATENIN; CITRATE SYNTHASE; CYCLOOXYGENASE 2; ENOLASE; EPIDERMAL GROWTH FACTOR; FATTY ACID SYNTHASE; FRUCTOSE 6 PHOSPHATE; GLUCOSE 6 PHOSPHATE DEHYDROGENASE; GLUCOSE TRANSPORTER 1; GLYCINE HYDROXYMETHYLTRANSFERASE; GLYCOSAMINOGLYCAN; HEXOKINASE; HYPOXIA INDUCIBLE FACTOR 1ALPHA; LACTATE DEHYDROGENASE; MITOGEN ACTIVATED PROTEIN KINASE 14; ORNITHINE DECARBOXYLASE; PROSTAGLANDIN E2; PROTEIN KINASE B; PROTEIN P53; PYRUVATE DEHYDROGENASE KINASE; SMAD4 PROTEIN; TRANSKETOLASE; TUMOR ANTIGEN; TUMOR SUPPRESSOR PROTEIN; UVOMORULIN; ANTINEOPLASTIC AGENT; FASN PROTEIN, HUMAN; FATTY ACID; TUMOR MARKER;

APOPTOSIS; ARTICLE; CANCER GROWTH; CELL METABOLISM; CELL PROLIFERATION; CELL SURVIVAL; CITRIC ACID CYCLE; DNA REPAIR; GLYCOLYSIS; HUMAN; LIPID METABOLISM; LIPOGENESIS; ONCOGENE K RAS; OXIDATIVE PHOSPHORYLATION; PANCREAS CANCER; PENTOSE PHOSPHATE CYCLE; POINT MUTATION; PROTEIN EXPRESSION; PYRIMIDINE SYNTHESIS; ANIMAL; CARCINOMA, PANCREATIC DUCTAL; DISEASE COURSE; DRUG EFFECTS; ENERGY METABOLISM; METABOLISM; PANCREATIC NEOPLASMS; PATHOLOGY; PREDICTIVE VALUE; TREATMENT OUTCOME;

ANIMALS; ANTINEOPLASTIC AGENTS; CARCINOMA, PANCREATIC DUCTAL; DISEASE PROGRESSION; ENERGY METABOLISM; FATTY ACID SYNTHASE, TYPE I; FATTY ACIDS; HUMANS; LIPOGENESIS; PANCREATIC NEOPLASMS; PREDICTIVE VALUE OF TESTS; TREATMENT OUTCOME; TUMOR MARKERS, BIOLOGICAL;

EID: 84895896123     PISSN: 10079327     EISSN: 22192840     Source Type: Journal    
DOI: 10.3748/wjg.v20.i9.2279     Document Type: Article

References (311)

1. Suvà ML, Riggi N, Bernstein BE. Epigenetic reprogramming in cancer. Science 2013; 339: 1567-1570 [PMID: 23539597 DOI: 10.1126/science.1230184]
2. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000; 100: 57-70 [PMID: 10647931 DOI: 10.1016/S0092-8674(00)81683-9]
3. Tennant DA, Durán RV, Boulahbel H, Gottlieb E. Metabolic transformation in cancer. Carcinogenesis 2009; 30: 1269-1280 [PMID: 19321800 DOI: 10.1093/carcin/bgp070]
4. Warburg O. The metabolism of tumors. London: Constable, 1930
5. Alo' PL, Visca P, Marci A, Mangoni A, Botti C, Di Tondo U. Expression of fatty acid synthase (FAS) as a predictor of recurrence in stage I breast carcinoma patients. Cancer 1996; 77: 474-482 [PMID: 8630954 DOI: 10.1002/(SICI)1097-0142(19 960201)]
6. Swinnen JV, Vanderhoydonc F, Elgamal AA, Eelen M, Vercaeren I, Joniau S, Van Poppel H, Baert L, Goossens K, Heyns W, Verhoeven G. Selective activation of the fatty acid synthesis pathway in human prostate cancer. Int J Cancer 2000; 88: 176-179 [PMID: 11004665]
7. Turyn J, Schlichtholz B, Dettlaff-Pokora A, Presler M, Goyke E, Matuszewski M, Kmieć Z, Krajka K, Swierczynski J. Increased activity of glycerol 3-phosphate dehydrogenase and other lipogenic enzymes in human bladder cancer. Horm Metab Res 2003; 35: 565-569 [PMID: 14605988 DOI: 10.1055/ s-2003-43500]
8. Kuhajda FP, Piantadosi S, Pasternack GR. Haptoglobinrelated protein (Hpr) epitopes in breast cancer as a predictor of recurrence of the disease. N Engl J Med 1989; 321: 636-641 [PMID: 2475778 DOI: 10.1056/NEJM198909073211003]
9. Kuhajda FP, Jenner K, Wood FD, Hennigar RA, Jacobs LB, Dick JD, Pasternack GR. Fatty acid synthesis: a potential selective target for antineoplastic therapy. Proc Natl Acad Sci USA 1994; 91: 6379-6383 [PMID: 8022791]
10. Alò PL, Visca P, Framarino ML, Botti C, Monaco S, Sebastiani V, Serpieri DE, Di Tondo U. Immunohistochemical study of fatty acid synthase in ovarian neoplasms. Oncol Rep 2000; 7: 1383-1388 [PMID: 11032949]
11. Rashid A, Pizer ES, Moga M, Milgraum LZ, Zahurak M, Pasternack GR, Kuhajda FP, Hamilton SR. Elevated expression of fatty acid synthase and fatty acid synthetic activity in colorectal neoplasia. Am J Pathol 1997; 150: 201-208 [PMID: 9006336]
12. Pizer ES, Lax SF, Kuhajda FP, Pasternack GR, Kurman RJ. Fatty acid synthase expression in endometrial carcinoma: correlation with cell proliferation and hormone receptors. Cancer 1998; 83: 528-537 [PMID: 9690546]
13. Boren J, Cascante M, Marin S, Comín-Anduix B, Centelles JJ, Lim S, Bassilian S, Ahmed S, Lee WN, Boros LG. Gleevec (STI571) influences metabolic enzyme activities and glucose carbon flow toward nucleic acid and fatty acid synthesis in myeloid tumor cells. J Biol Chem 2001; 276: 37747-37753 [PMID: 11489902 DOI: 10.1074/jbc.M105796200]
14. DeBerardinis RJ, Mancuso A, Daikhin E, Nissim I, Yudkoff M, Wehrli S, Thompson CB. Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc Natl Acad Sci USA 2007; 104: 19345-19350 [PMID: 18032601 DOI: 10.1073/pnas.0709747104]
15. Lee WN, Byerley LO, Bassilian S, Ajie HO, Clark I, Edmond J, Bergner EA. Isotopomer study of lipogenesis in human hepatoma cells in culture: contribution of carbon and hydrogen atoms from glucose. Anal Biochem 1995; 226: 100-112 [PMID: 7785761 DOI: 10.1006/abio.1995.1197]
16. Marin-Valencia I, Yang C, Mashimo T, Cho S, Baek H, Yang XL, Rajagopalan KN, Maddie M, Vemireddy V, Zhao Z, Cai L, Good L, Tu BP, Hatanpaa KJ, Mickey BE, Matés JM, Pascual JM, Maher EA, Malloy CR, Deberardinis RJ, Bachoo RM. Analysis of tumor metabolism reveals mitochondrial glucose oxidation in genetically diverse human glioblastomas in the mouse brain in vivo. Cell Metab 2012; 15: 827-837 [PMID: 22682223 DOI: 10.1016/j.cmet.2012.05.001]
17. Bauer DE, Hatzivassiliou G, Zhao F, Andreadis C, Thompson CB. ATP citrate lyase is an important component of cell growth and transformation. Oncogene 2005; 24: 6314-6322 [PMID: 16007201 DOI: 10.1038/sj.onc.1208773]
18. Hanai JI, Doro N, Seth P, Sukhatme VP. ATP citrate lyase knockdown impacts cancer stem cells in vitro. Cell Death Dis 2013; 4: e696 [PMID: 23807225 DOI: 10.1038/cddis.2013.215]
19. Schlichtholz B, Turyn J, Goyke E, Biernacki M, Jaskiewicz K, Sledzinski Z, Swierczynski J. Enhanced citrate synthase activity in human pancreatic cancer. Pancreas 2005; 30: 99-104 [PMID: 15714131]
20. Simonnet H, Alazard N, Pfeiffer K, Gallou C, Béroud C, Demont J, Bouvier R, Schägger H, Godinot C. Low mitochondrial respiratory chain content correlates with tumor aggressiveness in renal cell carcinoma. Carcinogenesis 2002; 23: 759-768 [PMID: 12016148 DOI: 10.1093/carcin/23.5.759]
21. Szutowicz A, Kwiatkowski J, Angielski S. Lipogenetic and glycolytic enzyme activities in carcinoma and nonmalignant diseases of the human breast. Br J Cancer 1979; 39: 681-687 [PMID: 444407]
22. Lu CW, Lin SC, Chen KF, Lai YY, Tsai SJ. Induction of pyruvate dehydrogenase kinase-3 by hypoxia-inducible factor-1 promotes metabolic switch and drug resistance. J Biol Chem 2008; 283: 28106-28114 [PMID: 18718909 DOI: 10.1074/jbc. M803508200]
23. Kim JW, Tchernyshyov I, Semenza GL, Dang CV. HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab 2006; 3: 177-185 [PMID: 16517405 DOI: 10.1016/ j.cmet.2006.02.002]
24. Kim JW, Gao P, Liu YC, Semenza GL, Dang CV. Hypoxiainducible factor 1 and dysregulated c-Myc cooperatively induce vascular endothelial growth factor and metabolic switches hexokinase 2 and pyruvate dehydrogenase kinase 1. Mol Cell Biol 2007; 27: 7381-7393 [PMID: 17785433 DOI: 10.1128/MCB.00440-07]
25. Hitosugi T, Fan J, Chung TW, Lythgoe K, Wang X, Xie J, Ge Q, Gu TL, Polakiewicz RD, Roesel JL, Chen GZ, Boggon TJ, Lonial S, Fu H, Khuri FR, Kang S, Chen J. Tyrosine phosphorylation of mitochondrial pyruvate dehydrogenase kinase 1 is important for cancer metabolism. Mol Cell 2011; 44: 864-877 [PMID: 22195962 DOI: 10.1016/j.molcel.2011.10.015]
26. Vizán P, Alcarraz-Vizán G, Díaz-Moralli S, Solovjeva ON, Frederiks WM, Cascante M. Modulation of pentose phosphate pathway during cell cycle progression in human colon adenocarcinoma cell line HT29. Int J Cancer 2009; 124: 2789-2796 [PMID: 19253370 DOI: 10.1002/ijc.24262]
27. Adrych K, Smoczynski M, Stojek M, Sledzinski T, Slominska E, Goyke E, Smolenski RT, Swierczynski J. Decreased serum essential and aromatic amino acids in patients with chronic pancreatitis. World J Gastroenterol 2010; 16: 4422-4427 [PMID: 20845509 DOI: 10.3748/wjg.v16.i35.4422]
28. Gatenby RA, Gillies RJ. Glycolysis in cancer: a potential target for therapy. Int J Biochem Cell Biol 2007; 39: 1358-1366 [PMID: 17499003 DOI: 10.1016/j.biocel.2007.03.021]
29. DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab 2008; 7: 11-20 [PMID: 18177721 DOI: 10.1016/j.cmet.2007.10.002]
30. Curi R, Lagranha CJ, Doi SQ, Sellitti DF, Procopio J, Pithon-Curi TC, Corless M, Newsholme P. Molecular mechanisms of glutamine action. J Cell Physiol 2005; 204: 392-401 [PMID: 15795900 DOI: 10.1002/jcp.20339]
31. Biswas S, Lunec J, Bartlett K. Non-glucose metabolism in cancer cells--is it all in the fat? Cancer Metastasis Rev 2012; 31: 689-698 [PMID: 22706846 DOI: 10.1007/s10555-012-9384-6]
32. Colombo SL, Palacios-Callender M, Frakich N, Carcamo S, Kovacs I, Tudzarova S, Moncada S. Molecular basis for the differential use of glucose and glutamine in cell proliferation as revealed by synchronized HeLa cells. Proc Natl Acad Sci USA 2011; 108: 21069-21074 [PMID: 22106309 DOI: 10.1073/ pnas.1117500108]
33. Choi SY, Collins CC, Gout PW, Wang Y. Cancer-generated lactic acid: a regulatory, immunosuppressive metabolite? J Pathol 2013; 230: 350-355 [PMID: 23729358 DOI: 10.1002/ path.4218]
34. Le A, Lane AN, Hamaker M, Bose S, Gouw A, Barbi J, Tsukamoto T, Rojas CJ, Slusher BS, Zhang H, Zimmerman LJ, Liebler DC, Slebos RJ, Lorkiewicz PK, Higashi RM, Fan TW, Dang CV. Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B cells. Cell Metab 2012; 15: 110-121 [PMID: 22225880 DOI: 10.1016/ j.cmet.2011.12.009]
35. Wellen KE, Lu C, Mancuso A, Lemons JM, Ryczko M, Dennis JW, Rabinowitz JD, Coller HA, Thompson CB. The hexosamine biosynthetic pathway couples growth factor-induced glutamine uptake to glucose metabolism. Genes Dev 2010; 24: 2784-2799 [PMID: 21106670 DOI: 10.1101/gad.1985910]
36. Metallo CM, Gameiro PA, Bell EL, Mattaini KR, Yang J, Hiller K, Jewell CM, Johnson ZR, Irvine DJ, Guarente L, Kelleher JK, Vander Heiden MG, Iliopoulos O, Stephanopoulos G. Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia. Nature 2012; 481: 380-384 [PMID: 22101433 DOI: 10.1038/nature10602]
37. Mullen AR, Wheaton WW, Jin ES, Chen PH, Sullivan LB, Cheng T, Yang Y, Linehan WM, Chandel NS, DeBerardinis RJ. Reductive carboxylation supports growth in tumour cells with defective mitochondria. Nature 2012; 481: 385-388 [PMID: 22101431 DOI: 10.1038/nature10642]
38. Wise DR, Ward PS, Shay JE, Cross JR, Gruber JJ, Sachdeva UM, Platt JM, DeMatteo RG, Simon MC, Thompson CB. Hypoxia promotes isocitrate dehydrogenase-dependent carboxylation of α-ketoglutarate to citrate to support cell growth and viability. Proc Natl Acad Sci USA 2011; 108: 19611-19616 [PMID: 22106302 DOI: 10.1073/pnas.1117773108]
39. Yoo H, Antoniewicz MR, Stephanopoulos G, Kelleher JK. Quantifying reductive carboxylation flux of glutamine to lipid in a brown adipocyte cell line. J Biol Chem 2008; 283: 20621-20627 [PMID: 18364355 DOI: 10.1074/jbc.M706494200]
40. Scott DA, Richardson AD, Filipp FV, Knutzen CA, Chiang GG, Ronai ZA, Osterman AL, Smith JW. Comparative metabolic flux profiling of melanoma cell lines: beyond the Warburg effect. J Biol Chem 2011; 286: 42626-42634 [PMID: 21998308 DOI: 10.1074/jbc.M111.282046]
41. Yuneva M, Zamboni N, Oefner P, Sachidanandam R, Lazebnik Y. Deficiency in glutamine but not glucose induces MYC-dependent apoptosis in human cells. J Cell Biol 2007; 178: 93-105 [PMID: 17606868 DOI: 10.1083/jcb.200703099]
42. Karbowska J, Kochan Z, Swierczynski J. Increase of lipogenic enzyme mRNA levels in rat white adipose tissue after multiple cycles of starvation-refeeding. Metabolism 2001; 50: 734-738 [PMID: 11398154 DOI: 10.1053/meta.2001.23309]
43. Korczynska J, Stelmanska E, Swierczynski J. Differential effect of long-term food restriction on fatty acid synthase and leptin gene expression in rat white adipose tissue. Horm Metab Res 2003; 35: 593-597 [PMID: 14605993 DOI: 10.1055/ s-2003-43505]
44. Stelmanska E, Korczynska J, Swierczynski J. Tissue-specific effect of refeeding after short-and long-term caloric restriction on malic enzyme gene expression in rat tissues. Acta Biochim Pol 2004; 51: 805-814 [PMID: 15448740]
45. Stelmanska E, Sucajtys-Szulc E, Korczynska J, Adrych K, Swierczynski J. Diversity of SREBP-1 gene expression in rat adipose tissue depots in response to refeeding after food restriction. Biochim Biophys Acta 2005; 1733: 130-136 [PMID: 15863360 DOI: 10.1016/j.bbalip.2004.12.004]
46. Nogalska A, Swierczynski J. Potential role of high serum leptin concentration in age-related decrease of fatty acid synthase gene expression in rat white adipose tissue. Exp Gerontol 2004; 39: 147-150 [PMID: 14724075 DOI: 10.1016/ j.exger.2003.09.013]
47. Nogalska A, Pankiewicz A, Goyke E, Swierczynski J. The age-related inverse relationship between ob and lipogenic enzymes genes expression in rat white adipose tissue. Exp Gerontol 2003; 38: 415-422 [PMID: 12670628 DOI: 10.1016/ S0531-5565(02)00210-3]
48. Nogalska A, Swierczynski J. The age-related differences in obese and fatty acid synthase gene expression in white adipose tissue of rat. Biochim Biophys Acta 2001; 1533: 73-80 [PMID: 11514238 DOI: 10.1016/S1388-1981(01)00142-1]
49. Swierczynski J, Goyke E, Wach L, Pankiewicz A, Kochan Z, Adamonis W, Sledzinski Z, Aleksandrowicz Z. Comparative study of the lipogenic potential of human and rat adipose tissue. Metabolism 2000; 49: 594-599 [PMID: 10831168 DOI: 10.1016/S0026-0495(00)80033-5]
50. Fritz V, Fajas L. Metabolism and proliferation share common regulatory pathways in cancer cells. Oncogene 2010; 29: 4369-4377 [PMID: 20514019 DOI: 10.1038/onc.2010.182]
51. Zhang XD, Qin ZH, Wang J. The role of p53 in cell metabolism. Acta Pharmacol Sin 2010; 31: 1208-1212 [PMID: 20729871 DOI: 10.1038/aps.2010.151]
52. Hu J, Liu Z, Wang X. Does TP53 mutation promote ovarian cancer metastasis to omentum by regulating lipid metabolism? Med Hypotheses 2013; 81: 515-520 [PMID: 23880140 DOI: 10.1016/j.mehy.2013.06.009]
53. Dang CV. MYC, metabolism, cell growth, and tumorigenesis. Cold Spring Harb Perspect Med 2013; 3: pii: a014217 [PMID: 23906881 DOI: 10.1101/cshperspect.a014217]
54. Wise DR, DeBerardinis RJ, Mancuso A, Sayed N, Zhang XY, Pfeiffer HK, Nissim I, Daikhin E, Yudkoff M, McMahon SB, Thompson CB. Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Proc Natl Acad Sci USA 2008; 105: 18782-18787 [PMID: 19033189 DOI: 10.1073/ pnas.0810199105]
55. Gao P, Tchernyshyov I, Chang TC, Lee YS, Kita K, Ochi T, Zeller KI, De Marzo AM, Van Eyk JE, Mendell JT, Dang CV. c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature 2009; 458: 762-765 [PMID: 19219026 DOI: 10.1038/nature07823]
56. Wang PY, Ma W, Park JY, Celi FS, Arena R, Choi JW, Ali QA, Tripodi DJ, Zhuang J, Lago CU, Strong LC, Talagala SL, Balaban RS, Kang JG, Hwang PM. Increased oxidative metabolism in the Li-Fraumeni syndrome. N Engl J Med 2013; 368: 1027-1032 [PMID: 23484829 DOI: 10.1056/NEJMoa1214091]
57. He Z, Liu H, Agostini M, Yousefi S, Perren A, Tschan MP, Mak TW, Melino G, Simon HU. p73 regulates autophagy and hepatocellular lipid metabolism through a transcriptional activation of the ATG5 gene. Cell Death Differ 2013; 20: 1415-1424 [PMID: 23912709 DOI: 10.1038/cdd.2013.104]
58. Porteiro B, Díaz-Ruíz A, Martínez G, Senra A, Vidal A, Serrano M, Gualillo O, López M, Malagón MM, Diéguez C, Nogueiras R. Ghrelin requires p53 to stimulate lipid storage in fat and liver. Endocrinology 2013; 154: 3671-3679 [PMID: 23832961 DOI: 10.1210/en.2013-1176]
59. Hu W, Zhang C, Wu R, Sun Y, Levine A, Feng Z. Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function. Proc Natl Acad Sci USA 2010; 107: 7455-7460 [PMID: 20378837 DOI: 10.1073/pnas.1001006107]
60. Suzuki S, Tanaka T, Poyurovsky MV, Nagano H, Mayama T, Ohkubo S, Lokshin M, Hosokawa H, Nakayama T, Suzuki Y, Sugano S, Sato E, Nagao T, Yokote K, Tatsuno I, Prives C. Phosphate-activated glutaminase (GLS2), a p53-inducible regulator of glutamine metabolism and reactive oxygen species. Proc Natl Acad Sci USA 2010; 107: 7461-7466 [PMID: 20351271 DOI: 10.1073/pnas.1002459107]
61. Daye D, Wellen KE. Metabolic reprogramming in cancer: unraveling the role of glutamine in tumorigenesis. Semin Cell Dev Biol 2012; 23: 362-369 [PMID: 22349059 DOI: 10.1016/ j.semcdb.2012.02.002]
62. Zhang C, Moore LM, Li X, Yung WK, Zhang W. IDH1/2 mutations target a key hallmark of cancer by deregulating cellular metabolism in glioma. Neuro Oncol 2013; 15: 1114-1126 [PMID: 23877318 DOI: 10.1093/neuonc/not087]
63. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127: 2893-2917 [PMID: 21351269 DOI: 10.1002/ijc.25516]
64. Tsutsumi K, Sato N, Tanabe R, Mizumoto K, Morimatsu K, Kayashima T, Fujita H, Ohuchida K, Ohtsuka T, Takahata S, Nakamura M, Tanaka M. Claudin-4 expression predicts survival in pancreatic ductal adenocarcinoma. Ann Surg Oncol 2012; 19 Suppl 3: S491-S499 [PMID: 21837532 DOI: 10.1245/ s10434-011-1970-2]
65. Sofuni A, Iijima H, Moriyasu F, Nakayama D, Shimizu M, Nakamura K, Itokawa F, Itoi T. Differential diagnosis of pan-creatic tumors using ultrasound contrast imaging. J Gastroenterol 2005; 40: 518-525 [PMID: 15942718 DOI: 10.1007/s00535-005-1578-z]
66. Koong AC, Mehta VK, Le QT, Fisher GA, Terris DJ, Brown JM, Bastidas AJ, Vierra M. Pancreatic tumors show high levels of hypoxia. Int J Radiat Oncol Biol Phys 2000; 48: 919-922 [PMID: 11072146]
67. Feig C, Gopinathan A, Neesse A, Chan DS, Cook N, Tuveson DA. The pancreas cancer microenvironment. Clin Cancer Res 2012; 18: 4266-4276 [PMID: 22896693 DOI: 10.1158/1078-0432. CCR-11-3114]
68. Majmundar AJ, Wong WJ, Simon MC. Hypoxia-inducible factors and the response to hypoxic stress. Mol Cell 2010; 40: 294-309 [PMID: 20965423 DOI: 10.1016/j.molcel.2010.09.022]
69. Pizzi S, Porzionato A, Pasquali C, Guidolin D, Sperti C, Fogar P, Macchi V, De Caro R, Pedrazzoli S, Parenti A. Glucose transporter-1 expression and prognostic significance in pancreatic carcinogenesis. Histol Histopathol 2009; 24: 175-185 [PMID: 19085834]
70. Kroemer G, Pouyssegur J. Tumor cell metabolism: cancer's Achilles' heel. Cancer Cell 2008; 13: 472-482 [PMID: 18538731 DOI: 10.1016/j.ccr.2008.05.005]
71. Natsuizaka M, Ozasa M, Darmanin S, Miyamoto M, Kondo S, Kamada S, Shindoh M, Higashino F, Suhara W, Koide H, Aita K, Nakagawa K, Kondo T, Asaka M, Okada F, Kobayashi M. Synergistic up-regulation of Hexokinase-2, glucose transporters and angiogenic factors in pancreatic cancer cells by glucose deprivation and hypoxia. Exp Cell Res 2007; 313: 3337-3348 [PMID: 17651733 DOI: 10.1016/j.yexcr.2007.06.013]
72. Rong Y, Wu W, Ni X, Kuang T, Jin D, Wang D, Lou W. Lactate dehydrogenase A is overexpressed in pancreatic cancer and promotes the growth of pancreatic cancer cells. Tumour Biol 2013; 34: 1523-1530 [PMID: 23404405 DOI: 10.1007/ s13277-013-0679-1]
73. Ying H, Kimmelman AC, Lyssiotis CA, Hua S, Chu GC, Fletcher-Sananikone E, Locasale JW, Son J, Zhang H, Coloff JL, Yan H, Wang W, Chen S, Viale A, Zheng H, Paik JH, Lim C, Guimaraes AR, Martin ES, Chang J, Hezel AF, Perry SR, Hu J, Gan B, Xiao Y, Asara JM, Weissleder R, Wang YA, Chin L, Cantley LC, DePinho RA. Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism. Cell 2012; 149: 656-670 [PMID: 22541435 DOI: 10.1016/j.cell.2012.01.058]
74. Dang CV, Semenza GL. Oncogenic alterations of metabolism. Trends Biochem Sci 1999; 24: 68-72 [PMID: 10098401 DOI: 10.1016/S0968-0004(98)01344-9]
75. Chun YS, Kim MS, Park JW. Oxygen-dependent and-independent regulation of HIF-1alpha. J Korean Med Sci 2002; 17: 581-588 [PMID: 12378005]
76. Kwon SJ, Song JJ, Lee YJ. Signal pathway of hypoxiainducible factor-1alpha phosphorylation and its interaction with von Hippel-Lindau tumor suppressor protein during ischemia in MiaPaCa-2 pancreatic cancer cells. Clin Cancer Res 2005; 11: 7607-7613 [PMID: 16278378 DOI: 10.1158/1078-0432.CCR-05-0981]
77. di Magliano MP, Logsdon CD. Roles for KRAS in pancreatic tumor development and progression. Gastroenterology 2013; 144: 1220-1229 [PMID: 23622131 DOI: 10.1053/ j.gastro.2013.01.071]
78. Macgregor-Das AM, Iacobuzio-Donahue CA. Molecular pathways in pancreatic carcinogenesis. J Surg Oncol 2013; 107: 8-14 [PMID: 22806689 DOI: 10.1002/jso.23213]
79. Foo WC, Rashid A, Wang H, Katz MH, Lee JE, Pisters PW, Wolff RA, Abbruzzese JL, Fleming JB, Wang H. Loss of phosphatase and tensin homolog expression is associated with recurrence and poor prognosis in patients with pancreatic ductal adenocarcinoma. Hum Pathol 2013; 44: 1024-1030 [PMID: 23260327 DOI: 10.1016/j.humpath.2012.09.001]
80. Melstrom LG, Salabat MR, Ding XZ, Milam BM, Strouch M, Pelling JC, Bentrem DJ. Apigenin inhibits the GLUT-1 glucose transporter and the phosphoinositide 3-kinase/Akt pathway in human pancreatic cancer cells. Pancreas 2008; 37: 426-431 [PMID: 18953257 DOI: 10.1097/ MPA.0b013e3181735ccb]
81. Zhang M, Ma Q, Hu H, Zhang D, Li J, Ma G, Bhat K, Wu E. Stem cell factor/c-kit signaling enhances invasion of pancreatic cancer cells via HIF-1α under normoxic condition. Cancer Lett 2011; 303: 108-117 [PMID: 21320746 DOI: 10.1016/ j.canlet.2011.01.017]
82. Skoudy A, Hernández-Muñoz I, Navarro P. Pancreatic ductal adenocarcinoma and transcription factors: role of c-Myc. J Gastrointest Cancer 2011; 42: 76-84 [PMID: 21279552 DOI: 10.1007/s12029-011-9258-0]
83. Hu HT, Ma QY, Zhang D, Shen SG, Han L, Ma YD, Li RF, Xie KP. HIF-1alpha links beta-adrenoceptor agonists and pancreatic cancer cells under normoxic condition. Acta Pharmacol Sin 2010; 31: 102-110 [PMID: 20037603 DOI: 10.1038/ aps.2009.181]
84. Wang L, Zhou W, Gou S, Wang T, Liu T, Wang C. Insulin promotes proliferative vitality and invasive capability of pancreatic cancer cells via hypoxia-inducible factor 1alpha pathway. J Huazhong Univ Sci Technolog Med Sci 2010; 30: 349-353 [PMID: 20556580 DOI: 10.1007/s11596-010-0355-2]
85. Chaika NV, Gebregiworgis T, Lewallen ME, Purohit V, Radhakrishnan P, Liu X, Zhang B, Mehla K, Brown RB, Caffrey T, Yu F, Johnson KR, Powers R, Hollingsworth MA, Singh PK. MUC1 mucin stabilizes and activates hypoxia-inducible factor 1 alpha to regulate metabolism in pancreatic cancer. Proc Natl Acad Sci USA 2012; 109: 13787-13792 [PMID: 22869720 DOI: 10.1073/pnas.1203339109]
86. Singh R, Bandyopadhyay D. MUC1: a target molecule for cancer therapy. Cancer Biol Ther 2007; 6: 481-486 [PMID: 18027437 DOI: 10.4161/cbt.6.4.4201]
87. Tsutsumida H, Swanson BJ, Singh PK, Caffrey TC, Kitajima S, Goto M, Yonezawa S, Hollingsworth MA. RNA interference suppression of MUC1 reduces the growth rate and metastatic phenotype of human pancreatic cancer cells. Clin Cancer Res 2006; 12: 2976-2987 [PMID: 16707592 DOI: 10.1158/1078-0432.CCR-05-1197]
88. Hamidi T, Cano CE, Grasso D, Garcia MN, Sandi MJ, Calvo EL, Dagorn JC, Lomberk G, Urrutia R, Goruppi S, Carracedo A, Velasco G, Iovanna JL. Nupr1-aurora kinase A pathway provides protection against metabolic stress-mediated autophagic-associated cell death. Clin Cancer Res 2012; 18: 5234-5246 [PMID: 22899799 DOI: 10.1158/1078-0432. CCR-12-0026]
89. Cano CE, Hamidi T, Sandi MJ, Iovanna JL. Nupr1: the Swissknife of cancer. J Cell Physiol 2011; 226: 1439-1443 [PMID: 20658514 DOI: 10.1002/jcp.22324]
90. Hamidi T, Algül H, Cano CE, Sandi MJ, Molejon MI, Riemann M, Calvo EL, Lomberk G, Dagorn JC, Weih F, Urrutia R, Schmid RM, Iovanna JL. Nuclear protein 1 promotes pancreatic cancer development and protects cells from stress by inhibiting apoptosis. J Clin Invest 2012; 122: 2092-2103 [PMID: 22565310 DOI: 10.1172/JCI60144]
91. Cano CE, Hamidi T, Garcia MN, Grasso D, Loncle C, Garcia S, Calvo E, Lomberk G, Dusetti N, Bartholin L, Urrutia R, Iovanna JL. Genetic inactivation of Nupr1 acts as a dominant suppressor event in a two-hit model of pancreatic carcinogenesis. Gut 2013; Epub ahead of print [PMID: 24026351 DOI: 10.1136/gutjnl-2013-305221]
92. Boros LG, Bassilian S, Lim S, Lee WN. Genistein inhibits nonoxidative ribose synthesis in MIA pancreatic adenocarcinoma cells: a new mechanism of controlling tumor growth. Pancreas 2001; 22: 1-7 [PMID: 11138960]
93. Boros LG, Lapis K, Szende B, Tömösközi-Farkas R, Balogh A, Boren J, Marin S, Cascante M, Hidvégi M. Wheat germ extract decreases glucose uptake and RNA ribose formation but increases fatty acid synthesis in MIA pancreatic adenocarcinoma cells. Pancreas 2001; 23: 141-147 [PMID: 11484916]
94. Son J, Lyssiotis CA, Ying H, Wang X, Hua S, Ligorio M, Perera RM, Ferrone CR, Mullarky E, Shyh-Chang N, Kang Y, Fleming JB, Bardeesy N, Asara JM, Haigis MC, DePinho RA, Cantley LC, Kimmelman AC. Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway. Nature 2013; 496: 101-105 [PMID: 23535601 DOI: 10.1038/nature12040]
95. Sabine JR, Kopelovich L, Abraham S, Morris HP. Control of lipid metabolism in hepatomas: conversion of glutamate carbon to fatty acid carbon via citrate in several transplantable hepatomas. Biochim Biophys Acta 1973; 296: 493-498 [PMID: 4347389]
96. Alo PL, Amini M, Piro F, Pizzuti L, Sebastiani V, Botti C, Murari R, Zotti G, Di Tondo U. Immunohistochemical expression and prognostic significance of fatty acid synthase in pancreatic carcinoma. Anticancer Res 2007; 27: 2523-2527 [PMID: 17695548]
97. Menendez JA, Lupu R. Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat Rev Cancer 2007; 7: 763-777 [PMID: 17882277 DOI: 10.1038/nrc2222]
98. Walter K, Hong SM, Nyhan S, Canto M, Fedarko N, Klein A, Griffith M, Omura N, Medghalchi S, Kuhajda F, Goggins M. Serum fatty acid synthase as a marker of pancreatic neoplasia. Cancer Epidemiol Biomarkers Prev 2009; 18: 2380-2385 [PMID: 19723916 DOI: 10.1158/1055-9965.EPI-09-0144]
99. Safran H, Iannitti D, Ramanathan R, Schwartz JD, Steinhoff M, Nauman C, Hesketh P, Rathore R, Wolff R, Tantravahi U, Hughes TM, Maia C, Pasquariello T, Goldstein L, King T, Tsai JY, Kennedy T. Herceptin and gemcitabine for metastatic pancreatic cancers that overexpress HER-2/neu. Cancer Invest 2004; 22: 706-712 [PMID: 15581051]
100. El-Rayes BF, Zalupski MM, Shields AF, Ferris AM, Vaishampayan U, Heilbrun LK, Venkatramanamoorthy R, Adsay V, Philip PA. A phase II study of celecoxib, gemcitabine, and cisplatin in advanced pancreatic cancer. Invest New Drugs 2005; 23: 583-590 [PMID: 16034525 DOI: 10.1007/s10637-005-1028-z]
101. Guais A, Baronzio G, Sanders E, Campion F, Mainini C, Fiorentini G, Montagnani F, Behzadi M, Schwartz L, Abolhassani M. Adding a combination of hydroxycitrate and lipoic acid (METABLOC™) to chemotherapy improves effectiveness against tumor development: experimental results and case report. Invest New Drugs 2012; 30: 200-211 [PMID: 20931262 DOI: 10.1007/s10637-010-9552-x]
102. Saha AK, Ruderman NB. Malonyl-CoA and AMP-activated protein kinase: an expanding partnership. Mol Cell Biochem 2003; 253: 65-70 [PMID: 14619957]
103. Adachi S, Yasuda I, Kawaguchi J, Yamauchi T, Nakashima M, Itani M, Nakamura M, Yoshioka T, Moriwaki H, Kozawa O. Ultraviolet enhances the sensitivity of pancreatic cancer cells to gemcitabine by activation of 5' AMP-activated protein kinase. Biochem Biophys Res Commun 2011; 414: 53-59 [PMID: 21945432 DOI: 10.1016/j.bbrc.2011.09.020]
104. Witkiewicz AK, Nguyen KH, Dasgupta A, Kennedy EP, Yeo CJ, Lisanti MP, Brody JR. Co-expression of fatty acid synthase and caveolin-1 in pancreatic ductal adenocarcinoma: implications for tumor progression and clinical outcome. Cell Cycle 2008; 7: 3021-3025 [PMID: 18802406 DOI: 10.4161/ cc.7.19.6719]
105. Yang Y, Liu H, Li Z, Zhao Z, Yip-Schneider M, Fan Q, Schmidt CM, Chiorean EG, Xie J, Cheng L, Chen JH, Zhang JT. Role of fatty acid synthase in gemcitabine and radiation resistance of pancreatic cancers. Int J Biochem Mol Biol 2011; 2: 89-98 [PMID: 21331354]
106. Bandyopadhyay S, Zhan R, Wang Y, Pai SK, Hirota S, Hosobe S, Takano Y, Saito K, Furuta E, Iiizumi M, Mohinta S, Watabe M, Chalfant C, Watabe K. Mechanism of apoptosis induced by the inhibition of fatty acid synthase in breast cancer cells. Cancer Res 2006; 66: 5934-5940 [PMID: 16740734 DOI: 10.1158/0008-5472.CAN-05-3197]
107. De Schrijver E, Brusselmans K, Heyns W, Verhoeven G, Swinnen JV. RNA interference-mediated silencing of the fatty acid synthase gene attenuates growth and induces morphological changes and apoptosis of LNCaP prostate cancer cells. Cancer Res 2003; 63: 3799-3804 [PMID: 12839976]
108. Lupu R, Menendez JA. Pharmacological inhibitors of Fatty Acid Synthase (FASN)--catalyzed endogenous fatty acid biogenesis: a new family of anti-cancer agents? Curr Pharm Biotechnol 2006; 7: 483-493 [PMID: 17168665 DOI: 10.2174/13 8920106779116928]
109. Pizer ES, Thupari J, Han WF, Pinn ML, Chrest FJ, Frehywot GL, Townsend CA, Kuhajda FP. Malonyl-coenzyme-A is a potential mediator of cytotoxicity induced by fatty-acid synthase inhibition in human breast cancer cells and xenografts. Cancer Res 2000; 60: 213-218 [PMID: 10667561]
110. Zecchin KG, Rossato FA, Raposo HF, Melo DR, Alberici LC, Oliveira HC, Castilho RF, Coletta RD, Vercesi AE, Graner E. Inhibition of fatty acid synthase in melanoma cells activates the intrinsic pathway of apoptosis. Lab Invest 2011; 91: 232-240 [PMID: 20805790 DOI: 10.1038/labinvest.2010.157]
111. Vazquez-Martin A, Colomer R, Brunet J, Lupu R, Menendez JA. Overexpression of fatty acid synthase gene activates HER1/HER2 tyrosine kinase receptors in human breast epithelial cells. Cell Prolif 2008; 41: 59-85 [PMID: 18211286 DOI: 10.1111/j.1365-2184.2007.00498.x]
112. Li N, Lu H, Chen C, Bu X, Huang P. Loss of fatty acid synthase inhibits the "HER2-PI3K/Akt axis" activity and malignant phenotype of Caco-2 cells. Lipids Health Dis 2013; 12: 83 [PMID: 23725225 DOI: 10.1186/1476-511X-12-83]
113. Choi WI, Jeon BN, Park H, Yoo JY, Kim YS, Koh DI, Kim MH, Kim YR, Lee CE, Kim KS, Osborne TF, Hur MW. Protooncogene FBI-1 (Pokemon) and SREBP-1 synergistically activate transcription of fatty-acid synthase gene (FASN). J Biol Chem 2008; 283: 29341-29354 [PMID: 18682402 DOI: 10.1074/ jbc.M802477200]
114. Rosin RD. Perspectives on this issue of the IJS. Int J Surg 2010; 8: 1 [PMID: 20080218 DOI: 10.1158/0008-5472.CAN-07-2489]
115. Bandyopadhyay S, Pai SK, Watabe M, Gross SC, Hirota S, Hosobe S, Tsukada T, Miura K, Saito K, Markwell SJ, Wang Y, Huggenvik J, Pauza ME, Iiizumi M, Watabe K. FAS expression inversely correlates with PTEN level in prostate cancer and a PI 3-kinase inhibitor synergizes with FAS siRNA to induce apoptosis. Oncogene 2005; 24: 5389-5395 [PMID: 15897909 DOI: 10.1038/sj.onc.1208555]
116. Yoon S, Lee MY, Park SW, Moon JS, Koh YK, Ahn YH, Park BW, Kim KS. Up-regulation of acetyl-CoA carboxylase alpha and fatty acid synthase by human epidermal growth factor receptor 2 at the translational level in breast cancer cells. J Biol Chem 2007; 282: 26122-26131 [PMID: 17631500 DOI: 10.1074/jbc.M702854200]
117. Menendez JA, Decker JP, Lupu R. In support of fatty acid synthase (FAS) as a metabolic oncogene: extracellular acidosis acts in an epigenetic fashion activating FAS gene expression in cancer cells. J Cell Biochem 2005; 94: 1-4 [PMID: 15523670 DOI: 10.1002/jcb.20310]
118. Wang TF, Wang H, Peng AF, Luo QF, Liu ZL, Zhou RP, Gao S, Zhou Y, Chen WZ. Inhibition of fatty acid synthase suppresses U-2 OS cell invasion and migration via downregulating the activity of HER2/PI3K/AKT signaling pathway in vitro. Biochem Biophys Res Commun 2013; 440: 229-234 [PMID: 24041695 DOI: 10.1016/j.bbrc.2013.09.024]
119. Morad SA, Messner MC, Levin JC, Abdelmageed N, Park H, Merrill AH, Cabot MC. Potential role of acid ceramidase in conversion of cytostatic to cytotoxic end-point in pancreatic cancer cells. Cancer Chemother Pharmacol 2013; 71: 635-645 [PMID: 23263160 DOI: 10.1007/s00280-012-2050-4]
120. Vandhana S, Coral K, Jayanthi U, Deepa PR, Krishnakumar S. Biochemical changes accompanying apoptotic cell death in retinoblastoma cancer cells treated with lipogenic enzyme inhibitors. Biochim Biophys Acta 2013; 1831: 1458-1466 [PMID: 23816424 DOI: 10.1016/j.bbalip.2013.06.005]
121. Vizan P, Boros LG, Figueras A, Capella G, Mangues R, Bassilian S, Lim S, Lee WN, Cascante M. K-ras codonspecific mutations produce distinctive metabolic phenotypes in NIH3T3 mice [corrected] fibroblasts. Cancer Res 2005; 65: 5512-5515 [PMID: 15994921 DOI: 10.1158/0008-5472. CAN-05-0074]
122. Weinberg F, Hamanaka R, Wheaton WW, Weinberg S, Joseph J, Lopez M, Kalyanaraman B, Mutlu GM, Budinger GR, Chandel NS. Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity. Proc Natl Acad Sci USA 2010; 107: 8788-8793 [PMID: 20421486 DOI: 10.1073/pnas.1003428107]
123. Boros LG, Lerner MR, Morgan DL, Taylor SL, Smith BJ, Postier RG, Brackett DJ. [1,2-13C2]-D-glucose profiles of the serum, liver, pancreas, and DMBA-induced pancreatic tumors of rats. Pancreas 2005; 31: 337-343 [PMID: 16258367]
124. Jiang P, Du W, Wang X, Mancuso A, Gao X, Wu M, Yang X. p53 regulates biosynthesis through direct inactivation of glucose-6-phosphate dehydrogenase. Nat Cell Biol 2011; 13: 310-316 [PMID: 21336310 DOI: 10.1038/ncb2172]
125. Zadra G, Photopoulos C, Loda M. The fat side of prostate cancer. Biochim Biophys Acta 2013; 1831: 1518-1532 [PMID: 23562839 DOI: 10.1016/j.bbalip.2013.03.010]
126. Rysman E, Brusselmans K, Scheys K, Timmermans L, Derua R, Munck S, Van Veldhoven PP, Waltregny D, Daniëls VW, Machiels J, Vanderhoydonc F, Smans K, Waelkens E, Verhoeven G, Swinnen JV. De novo lipogenesis protects cancer cells from free radicals and chemotherapeutics by promoting membrane lipid saturation. Cancer Res 2010; 70: 8117-8126 [PMID: 20876798 DOI: 10.1158/0008-5472.CAN-09-3871]
127. Fritz V, Benfodda Z, Rodier G, Henriquet C, Iborra F, Avancès C, Allory Y, de la Taille A, Culine S, Blancou H, Cristol JP, Michel F, Sardet C, Fajas L. Abrogation of de novo lipogenesis by stearoyl-CoA desaturase 1 inhibition interferes with oncogenic signaling and blocks prostate cancer progression in mice. Mol Cancer Ther 2010; 9: 1740-1754 [PMID: 20530718 DOI: 10.1158/1535-7163.MCT-09-1064]
128. Macášek J, Vecka M, Žák A, Urbánek M, Krechler T, Petruželka L, Staňková B, Zeman M. Plasma fatty acid composition in patients with pancreatic cancer: correlations to clinical parameters. Nutr Cancer 2012; 64: 946-955 [PMID: 23061902 DOI: 10.1080/01635581.2012.716138]
129. Michel V, Bakovic M. Lipid rafts in health and disease. Biol Cell 2007; 99: 129-140 [PMID: 17064251 DOI: 10.1042/ BC20060051]
130. Patlolla JM, Swamy MV, Raju J, Rao CV. Overexpression of caveolin-1 in experimental colon adenocarcinomas and human colon cancer cell lines. Oncol Rep 2004; 11: 957-963 [PMID: 15069532]
131. Kim HA, Kim KH, Lee RA. Expression of caveolin-1 is correlated with Akt-1 in colorectal cancer tissues. Exp Mol Pathol 2006; 80: 165-170 [PMID: 16202996 DOI: 10.1016/ j.yexmp.2005.09.001]
132. Fiucci G, Ravid D, Reich R, Liscovitch M. Caveolin-1 inhibits anchorage-independent growth, anoikis and invasiveness in MCF-7 human breast cancer cells. Oncogene 2002; 21: 2365-2375 [PMID: 11948420 DOI: 10.1038/sj.onc.1205300]
133. Fong A, Garcia E, Gwynn L, Lisanti MP, Fazzari MJ, Li M. Expression of caveolin-1 and caveolin-2 in urothelial carcinoma of the urinary bladder correlates with tumor grade and squamous differentiation. Am J Clin Pathol 2003; 120: 93-100 [PMID: 12866378 DOI: 10.1309/292N-HAYN-WAVR-EJ37]
134. Kato K, Hida Y, Miyamoto M, Hashida H, Shinohara T, Itoh T, Okushiba S, Kondo S, Katoh H. Overexpression of caveolin-1 in esophageal squamous cell carcinoma correlates with lymph node metastasis and pathologic stage. Cancer 2002; 94: 929-933 [PMID: 11920460 DOI: 10.1002/cncr.10329]
135. Li L, Yang G, Ebara S, Satoh T, Nasu Y, Timme TL, Ren C, Wang J, Tahir SA, Thompson TC. Caveolin-1 mediates testosterone-stimulated survival/clonal growth and promotes metastatic activities in prostate cancer cells. Cancer Res 2001; 61: 4386-4392 [PMID: 11389065]
136. Rakheja D, Kapur P, Hoang MP, Roy LC, Bennett MJ. Increased ratio of saturated to unsaturated C18 fatty acids in colonic adenocarcinoma: implications for cryotherapy and lipid raft function. Med Hypotheses 2005; 65: 1120-1123 [PMID: 16084671 DOI: 10.1016/j.mehy.2005.05.045]
137. Suzuoki M, Miyamoto M, Kato K, Hiraoka K, Oshikiri T, Nakakubo Y, Fukunaga A, Shichinohe T, Shinohara T, Itoh T, Kondo S, Katoh H. Impact of caveolin-1 expression on prognosis of pancreatic ductal adenocarcinoma. Br J Cancer 2002; 87: 1140-1144 [PMID: 12402154 DOI: 10.1038/sj.bjc.6600619]
138. Louie SM, Roberts LS, Mulvihill MM, Luo K, Nomura DK. Cancer cells incorporate and remodel exogenous palmitate into structural and oncogenic signaling lipids. Biochim Biophys Acta 2013; 1831: 1566-1572 [PMID: 23872477 DOI: 10.1016/j.bbalip.2013.07.008]
139. Kuemmerle NB, Rysman E, Lombardo PS, Flanagan AJ, Lipe BC, Wells WA, Pettus JR, Froehlich HM, Memoli VA, Morganelli PM, Swinnen JV, Timmerman LA, Chaychi L, Fricano CJ, Eisenberg BL, Coleman WB, Kinlaw WB. Lipoprotein lipase links dietary fat to solid tumor cell proliferation. Mol Cancer Ther 2011; 10: 427-436 [PMID: 21282354 DOI: 10.1158/1535-7163.MCT-10-0802]
140. Zaidi N, Lupien L, Kuemmerle NB, Kinlaw WB, Swinnen JV, Smans K. Lipogenesis and lipolysis: the pathways exploited by the cancer cells to acquire fatty acids. Prog Lipid Res 2013; 52: 585-589 [PMID: 24001676 DOI: 10.1016/ j.plipres.2013.08.005]
141. Swierczynski J, Sledzinski T. The role of adipokines and gastrointestinal tract hormones in obesity. In: Karcz WK, Thomusch O. Principles of metabolic surgery. Berlin Heidelberg: Spriger, 2012: 53-79
142. Chung YT, Matkowskyj KA, Li H, Bai H, Zhang W, Tsao MS, Liao J, Yang GY. Overexpression and oncogenic function of aldo-keto reductase family 1B10 (AKR1B10) in pancreatic carcinoma. Mod Pathol 2012; 25: 758-766 [PMID: 22222635 DOI: 10.1038/modpathol.2011.191]
143. Gallego O, Ruiz FX, Ardèvol A, Domínguez M, Alvarez R, de Lera AR, Rovira C, Farrés J, Fita I, Parés X. Structural basis for the high all-trans-retinaldehyde reductase activity of the tumor marker AKR1B10. Proc Natl Acad Sci USA 2007; 104: 20764-20769 [PMID: 18087047 DOI: 10.1073/ pnas.0705659105]
144. Quinn AM, Harvey RG, Penning TM. Oxidation of PAH trans-dihydrodiols by human aldo-keto reductase AKR1B10. Chem Res Toxicol 2008; 21: 2207-2215 [PMID: 18788756 DOI: 10.1021/tx8002005]
145. Endo S, Matsunaga T, Mamiya H, Ohta C, Soda M, Kitade Y, Tajima K, Zhao HT, El-Kabbani O, Hara A. Kinetic studies of AKR1B10, human aldose reductase-like protein: endogenous substrates and inhibition by steroids. Arch Biochem Biophys 2009; 487: 1-9 [PMID: 19464995 DOI: 10.1016/ j.abb.2009.05.009]
146. Martin HJ, Maser E. Role of human aldo-keto-reductase AKR1B10 in the protection against toxic aldehydes. Chem Biol Interact 2009; 178: 145-150 [PMID: 19013440 DOI: 10.1016/j.cbi.2008.10.021]
147. Fukumoto S, Yamauchi N, Moriguchi H, Hippo Y, Watanabe A, Shibahara J, Taniguchi H, Ishikawa S, Ito H, Yamamoto S, Iwanari H, Hironaka M, Ishikawa Y, Niki T, Sohara Y, Kodama T, Nishimura M, Fukayama M, Dosaka-Akita H, Aburatani H. Overexpression of the aldo-keto reductase family protein AKR1B10 is highly correlated with smokers' non-small cell lung carcinomas. Clin Cancer Res 2005; 11: 1776-1785 [PMID: 15755999 DOI: 10.1158/1078-0432. CCR-04-1238]
148. Ma J, Yan R, Zu X, Cheng JM, Rao K, Liao DF, Cao D. Aldoketo reductase family 1 B10 affects fatty acid synthesis by regulating the stability of acetyl-CoA carboxylase-alpha in breast cancer cells. J Biol Chem 2008; 283: 3418-3423 [PMID: 18056116 DOI: 10.1074/jbc.M707650200]
149. Novelli G, D'Apice MR. Protein farnesylation and disease. J Inherit Metab Dis 2012; 35: 917-926 [PMID: 22307208 DOI: 10.1007/s10545-011-9445-y]
150. Osmak M. Statins and cancer: current and future prospects. Cancer Lett 2012; 324: 1-12 [PMID: 22542807 DOI: 10.1016/ j.canlet.2012.04.011]
151. Jackson L, Evers BM. Chronic inflammation and pathogenesis of GI and pancreatic cancers. Cancer Treat Res 2006; 130: 39-65 [PMID: 16610702 DOI: 10.1007/0-387-26283-0_2]
152. Lipton A, Campbell-Baird C, Witters L, Harvey H, Ali S. Phase II trial of gemcitabine, irinotecan, and celecoxib in patients with advanced pancreatic cancer. J Clin Gastroenterol 2010; 44: 286-288 [PMID: 20216081 DOI: 10.1097/ MCG.0b013e3181cda097]
153. Merati K, Siadaty M, Andea A, Sarkar F, Ben-Josef E, Mohammad R, Philip P, Shields AF, Vaitkevicius V, Grignon DJ, Adsay NV. Expression of inflammatory modulator COX-2 in pancreatic ductal adenocarcinoma and its relationship to pathologic and clinical parameters. Am J Clin Oncol 2001; 24: 447-452 [PMID: 11586094]
154. Yip-Schneider MT, Barnard DS, Billings SD, Cheng L, Heilman DK, Lin A, Marshall SJ, Crowell PL, Marshall MS, Sweeney CJ. Cyclooxygenase-2 expression in human pancreatic adenocarcinomas. Carcinogenesis 2000; 21: 139-146 [PMID: 10657949 DOI: 10.1093/carcin/21.2.139]
155. Ding XZ, Hennig R, Adrian TE. Lipoxygenase and cyclooxygenase metabolism: new insights in treatment and chemoprevention of pancreatic cancer. Mol Cancer 2003; 2: 10 [PMID: 12575899 DOI: 10.1186/1476-4598-2-10]
156. Molina MA, Sitja-Arnau M, Lemoine MG, Frazier ML, Sinicrope FA. Increased cyclooxygenase-2 expression in human pancreatic carcinomas and cell lines: growth inhibition by nonsteroidal anti-inflammatory drugs. Cancer Res 1999; 59: 4356-4362 [PMID: 10485483]
157. Peulen O, Gonzalez A, Peixoto P, Turtoi A, Mottet D, Delvenne P, Castronovo V. The anti-tumor effect of HDAC inhibition in a human pancreas cancer model is significantly improved by the simultaneous inhibition of cyclooxygenase 2. PLoS One 2013; 8: e75102 [PMID: 24040391 DOI: 10.1371/ journal.pone.0075102]
158. Wu Y, Antony S, Meitzler JL, Doroshow JH. Molecular mechanisms underlying chronic inflammation-associated cancers. Cancer Lett 2013; Epub ahead of print [PMID: 23988267 DOI: 10.1016/j.canlet.2013.08.014]
159. Migita T, Ruiz S, Fornari A, Fiorentino M, Priolo C, Zadra G, Inazuka F, Grisanzio C, Palescandolo E, Shin E, Fiore C, Xie W, Kung AL, Febbo PG, Subramanian A, Mucci L, Ma J, Signoretti S, Stampfer M, Hahn WC, Finn S, Loda M. Fatty acid synthase: a metabolic enzyme and candidate oncogene in prostate cancer. J Natl Cancer Inst 2009; 101: 519-532 [PMID: 19318631 DOI: 10.1093/jnci/djp030]
160. Gao Y, Lin LP, Zhu CH, Chen Y, Hou YT, Ding J. Growth arrest induced by C75, A fatty acid synthase inhibitor, was partially modulated by p38 MAPK but not by p53 in human hepatocellular carcinoma. Cancer Biol Ther 2006; 5: 978-985 [PMID: 16855382 DOI: 10.4161/cbt.5.8.2883]
161. Knowles LM, Axelrod F, Browne CD, Smith JW. A fatty acid synthase blockade induces tumor cell-cycle arrest by downregulating Skp2. J Biol Chem 2004; 279: 30540-30545 [PMID: 15138278 DOI: 10.1074/jbc.M405061200]
162. Morikawa K, Ikeda C, Nonaka M, Suzuki I. Growth arrest and apoptosis induced by quercetin is not linked to adipogenic conversion of human preadipocytes. Metabolism 2007; 56: 1656-1665 [PMID: 17998018 DOI: 10.1016/ j.metabol.2007.07.008]
163. Pizer ES, Chrest FJ, DiGiuseppe JA, Han WF. Pharmacological inhibitors of mammalian fatty acid synthase suppress DNA replication and induce apoptosis in tumor cell lines. Cancer Res 1998; 58: 4611-4615 [PMID: 9788612]
164. Knowles LM, Smith JW. Genome-wide changes accompanying knockdown of fatty acid synthase in breast cancer. BMC Genomics 2007; 8: 168 [PMID: 17565694 DOI: 10.1186/1471-2164-8-168]
165. Liu H, Liu Y, Zhang JT. A new mechanism of drug resistance in breast cancer cells: fatty acid synthase overexpression-mediated palmitate overproduction. Mol Cancer Ther 2008; 7: 263-270 [PMID: 18281512 DOI: 10.1158/1535-7163. MCT-07-0445]
166. Alò PL, Visca P, Trombetta G, Mangoni A, Lenti L, Monaco S, Botti C, Serpieri DE, Di Tondo U. Fatty acid synthase (FAS) predictive strength in poorly differentiated early breast carcinomas. Tumori 1999; 85: 35-40 [PMID: 10228495]
167. Shurbaji MS, Kalbfleisch JH, Thurmond TS. Immunohistochemical detection of a fatty acid synthase (OA-519) as a predictor of progression of prostate cancer. Hum Pathol 1996; 27: 917-921 [PMID: 8816886 DOI: 10.1016/S0046-8177(96)90218-X]
168. Innocenzi D, Alò PL, Balzani A, Sebastiani V, Silipo V, La Torre G, Ricciardi G, Bosman C, Calvieri S. Fatty acid synthase expression in melanoma. J Cutan Pathol 2003; 30: 23-28 [PMID: 12534800 DOI: 10.1034/j.1600-0560.2003.300104.x]
169. Camassei FD, Jenkner A, Ravà L, Bosman C, Francalanci P, Donfrancesco A, Alò PL, Boldrini R. Expression of the lipogenic enzyme fatty acid synthase (FAS) as a predictor of poor outcome in nephroblastoma: an interinstitutional study. Med Pediatr Oncol 2003; 40: 302-308 [PMID: 12652618 DOI: 10.1002/mpo.10274]
170. Horiguchi A, Asano T, Asano T, Ito K, Sumitomo M, Hayakawa M. Pharmacological inhibitor of fatty acid synthase suppresses growth and invasiveness of renal cancer cells. J Urol 2008; 180: 729-736 [PMID: 18555493 DOI: 10.1016/ j.juro.2008.03.186]
171. Sebastiani V, Visca P, Botti C, Santeusanio G, Galati GM, Piccini V, Capezzone de Joannon B, Di Tondo U, Alo PL. Fatty acid synthase is a marker of increased risk of recurrence in endometrial carcinoma. Gynecol Oncol 2004; 92: 101-105 [PMID: 14751145 DOI: 10.1016/j.ygyno.2003.10.027]
172. Ogino S, Nosho K, Meyerhardt JA, Kirkner GJ, Chan AT, Kawasaki T, Giovannucci EL, Loda M, Fuchs CS. Cohort study of fatty acid synthase expression and patient survival in colon cancer. J Clin Oncol 2008; 26: 5713-5720 [PMID: 18955444 DOI: 10.1200/JCO.2008.18.2675]
173. Gansler TS, Hardman W, Hunt DA, Schaffel S, Hennigar RA. Increased expression of fatty acid synthase (OA-519) in ovarian neoplasms predicts shorter survival. Hum Pathol 1997; 28: 686-692 [PMID: 9191002 DOI: 10.1016/ S0046-8177(97)90177-5]
174. Piyathilake CJ, Frost AR, Manne U, Bell WC, Weiss H, Heimburger DC, Grizzle WE. The expression of fatty acid synthase (FASE) is an early event in the development and progression of squamous cell carcinoma of the lung. Hum Pathol 2000; 31: 1068-1073 [PMID: 11014573 DOI: 10.1053/ hupa.2000.9842]
175. Silva SD, Agostini M, Nishimoto IN, Coletta RD, Alves FA, Lopes MA, Kowalski LP, Graner E. Expression of fatty acid synthase, ErbB2 and Ki-67 in head and neck squamous cell carcinoma. A clinicopathological study. Oral Oncol 2004; 40: 688-696 [PMID: 15172638 DOI: 10.1016/j.oraloncology.2004.0 1.004]
176. Silva SD, Perez DE, Nishimoto IN, Alves FA, Pinto CA, Kowalski LP, Graner E. Fatty acid synthase expression in squamous cell carcinoma of the tongue: clinicopathological findings. Oral Dis 2008; 14: 376-382 [PMID: 18410580 DOI: 10.1111/j.1601-0825.2007.01395.x]
177. Orian-Rousseau V. CD44, a therapeutic target for metastasising tumours. Eur J Cancer 2010; 46: 1271-1277 [PMID: 20303742 DOI: 10.1016/j.ejca.2010.02.024]
178. Trusolino L, Bertotti A, Comoglio PM. MET signalling: principles and functions in development, organ regeneration and cancer. Nat Rev Mol Cell Biol 2010; 11: 834-848 [PMID: 21102609 DOI: 10.1038/nrm3012]
179. Orian-Rousseau V, Chen L, Sleeman JP, Herrlich P, Ponta H. CD44 is required for two consecutive steps in HGF/c-Met signaling. Genes Dev 2002; 16: 3074-3086 [PMID: 12464636 DOI: 10.1101/gad.242602]
180. Zaytseva YY, Rychahou PG, Gulhati P, Elliott VA, Mustain WC, O'Connor K, Morris AJ, Sunkara M, Weiss HL, Lee EY, Evers BM. Inhibition of fatty acid synthase attenuates CD44-associated signaling and reduces metastasis in colorectal cancer. Cancer Res 2012; 72: 1504-1517 [PMID: 22266115 DOI: 10.1158/0008-5472.CAN-11-4057]
181. Uddin S, Hussain AR, Ahmed M, Bu R, Ahmed SO, Ajarim D, Al-Dayel F, Bavi P, Al-Kuraya KS. Inhibition of fatty acid synthase suppresses c-Met receptor kinase and induces apoptosis in diffuse large B-cell lymphoma. Mol Cancer Ther 2010; 9: 1244-1255 [PMID: 20423996 DOI: 10.1158/1535-7163. MCT-09-1061]
182. Coleman DT, Bigelow R, Cardelli JA. Inhibition of fatty acid synthase by luteolin post-transcriptionally down-regulates c-Met expression independent of proteosomal/lysosomal degradation. Mol Cancer Ther 2009; 8: 214-224 [PMID: 19139131]
183. Menendez JA, Colomer R, Lupu R. Inhibition of tumorassociated fatty acid synthase activity enhances vinorelbine (Navelbine)-induced cytotoxicity and apoptotic cell death in human breast cancer cells. Oncol Rep 2004; 12: 411-422 [PMID: 15254710]
184. Menendez JA, Lupu R, Colomer R. Inhibition of tumor-associated fatty acid synthase hyperactivity induces synergistic chemosensitization of HER-2/ neu-overexpressing human breast cancer cells to docetaxel (taxotere). Breast Cancer Res Treat 2004; 84: 183-195 [PMID: 14999148]
185. Menendez JA, Vellon L, Colomer R, Lupu R. Pharmacological and small interference RNA-mediated inhibition of breast cancer-associated fatty acid synthase (oncogenic antigen-519) synergistically enhances Taxol (paclitaxel)-induced cytotoxicity. Int J Cancer 2005; 115: 19-35 [PMID: 15657900 DOI: 10.1002/ijc.20754]
186. Vazquez-Martin A, Ropero S, Brunet J, Colomer R, Menendez JA. Inhibition of Fatty Acid Synthase (FASN) synergistically enhances the efficacy of 5-fluorouracil in breast carcinoma cells. Oncol Rep 2007; 18: 973-980 [PMID: 17786362]
187. Menendez JA, Vellon L, Lupu R. The antiobesity drug Orlistat induces cytotoxic effects, suppresses Her-2/neu (erbB-2) oncogene overexpression, and synergistically interacts with trastuzumab (Herceptin) in chemoresistant ovarian cancer cells. Int J Gynecol Cancer 2006; 16: 219-221 [PMID: 16445636 DOI: 10.1111/j.1525-1438.2006.00297.x]
188. Haglund C, Roberts PJ, Kuusela P, Scheinin TM, Mäkelä O, Jalanko H. Evaluation of CA 19-9 as a serum tumour marker in pancreatic cancer. Br J Cancer 1986; 53: 197-202 [PMID: 3456787 DOI: 10.1038/bjc.1986.35]
189. Duffy MJ. CA 19-9 as a marker for gastrointestinal cancers: a review. Ann Clin Biochem 1998; 35 (Pt 3): 364-370 [PMID: 9635101 DOI: 10.1177/000456329803500304]
190. Sandblom G, Granroth S, Rasmussen IC. TPS, CA 19-9, VEGF-A, and CEA as diagnostic and prognostic factors in patients with mass lesions in the pancreatic head. Ups J Med Sci 2008; 113: 57-64 [PMID: 18521799]
191. Wang J, Chen J, Chang P, LeBlanc A, Li D, Abbruzzesse JL, Frazier ML, Killary AM, Sen S. MicroRNAs in plasma of pancreatic ductal adenocarcinoma patients as novel blood-based biomarkers of disease. Cancer Prev Res (Phila) 2009; 2: 807-813 [PMID: 19723895 DOI: 10.1158/1940-6207.CAPR-09-0094]
192. Yabushita S, Fukamachi K, Tanaka H, Sumida K, Deguchi Y, Sukata T, Kawamura S, Uwagawa S, Suzui M, Tsuda H. Circulating microRNAs in serum of human K-ras oncogene transgenic rats with pancreatic ductal adenocarcinomas. Pancreas 2012; 41: 1013-1018 [PMID: 22513294 DOI: 10.1097/ MPA.0b013e31824ac3a5]
193. Sitek B, Sipos B, Alkatout I, Poschmann G, Stephan C, Schulenborg T, Marcus K, Lüttges J, Dittert DD, Baretton G, Schmiegel W, Hahn SA, Klöppel G, Meyer HE, Stühler K. Analysis of the pancreatic tumor progression by a quantitative proteomic approach and immunhistochemical validation. J Proteome Res 2009; 8: 1647-1656 [PMID: 19714807 DOI: 10.1021/pr800890j]
194. Yabushita S, Fukamachi K, Kikuchi F, Ozaki M, Miyata K, Sukata T, Deguchi Y, Tanaka H, Kakehashi A, Kawamura S, Uwagawa S, Wanibuchi H, Suzui M, Alexander DB, Tsuda H. Twenty-one proteins up-regulated in human H-ras oncogene transgenic rat pancreas cancers are up-regulated in human pancreas cancer. Pancreas 2013; 42: 1034-1039 [PMID: 23648844 DOI: 10.1097/MPA.0b013e3182883624]
195. Wang Y, Kuhajda FP, Sokoll LJ, Chan DW. Two-site ELISA for the quantitative determination of fatty acid synthase. Clin Chim Acta 2001; 304: 107-115 [PMID: 11165205 DOI: 10.1016/ S0009-8981(00)00404-6]
196. Wang Y, Kuhajda FP, Li JN, Pizer ES, Han WF, Sokoll LJ, Chan DW. Fatty acid synthase (FAS) expression in human breast cancer cell culture supernatants and in breast cancer patients. Cancer Lett 2001; 167: 99-104 [PMID: 11323104 DOI: 10.1016/S0304-3835(01)00464-5]
197. Wang YY, Kuhajda FP, Li J, Finch TT, Cheng P, Koh C, Li T, Sokoll LJ, Chan DW. Fatty acid synthase as a tumor marker: its extracellular expression in human breast cancer. J Exp Ther Oncol 2004; 4: 101-110 [PMID: 15500005]
198. Notarnicola M, Tutino V, Calvani M, Lorusso D, Guerra V, Caruso MG. Serum levels of fatty acid synthase in colorectal cancer patients are associated with tumor stage. J Gastrointest Cancer 2012; 43: 508-511 [PMID: 21727995 DOI: 10.1007/ s12029-011-9300-2]
199. Yabushita S, Fukamachi K, Tanaka H, Fukuda T, Sumida K, Deguchi Y, Mikata K, Nishioka K, Kawamura S, Uwagawa S, Suzui M, Alexander DB, Tsuda H. Metabolomic and transcriptomic profiling of human K-ras oncogene transgenic rats with pancreatic ductal adenocarcinomas. Carcinogenesis 2013; 34: 1251-1259 [PMID: 23393225 DOI: 10.1093/carcin/ bgt053]
200. von Roemeling CA, Marlow LA, Wei JJ, Cooper SJ, Caulfield TR, Wu K, Tan WW, Tun HW, Copland JA. Stearoyl-CoA desaturase 1 is a novel molecular therapeutic target for clear cell renal cell carcinoma. Clin Cancer Res 2013; 19: 2368-2380 [PMID: 23633458 DOI: 10.1158/1078-0432.CCR-12-3249]
201. Chavarro JE, Kenfield SA, Stampfer MJ, Loda M, Campos H, Sesso HD, Ma J. Blood levels of saturated and monounsaturated fatty acids as markers of de novo lipogenesis and risk of prostate cancer. Am J Epidemiol 2013; 178: 1246-1255 [PMID: 23989197 DOI: 10.1093/aje/kwt136]
202. Zhang L, Jin H, Guo X, Yang Z, Zhao L, Tang S, Mo P, Wu K, Nie Y, Pan Y, Fan D. Distinguishing pancreatic cancer from chronic pancreatitis and healthy individuals by (1)H nuclear magnetic resonance-based metabonomic profiles. Clin Biochem 2012; 45: 1064-1069 [PMID: 22613268 DOI: 10.1016/j.cli nbiochem.2012.05.012]
203. Urayama S, Zou W, Brooks K, Tolstikov V. Comprehensive mass spectrometry based metabolic profiling of blood plasma reveals potent discriminatory classifiers of pancreatic cancer. Rapid Commun Mass Spectrom 2010; 24: 613-620 [PMID: 20143319 DOI: 10.1002/rcm.4420]
204. Czernin J, Benz MR, Allen-Auerbach MS. PET Imaging of Prostate Cancer Using C-Acetate. PET Clin 2009; 4: 163-172 [PMID: 21984877 DOI: 10.1016/j.cpet.2009.05.001]
205. Fox JJ, Schöder H, Larson SM. Molecular imaging of prostate cancer. Curr Opin Urol 2012; 22: 320-327 [PMID: 22617062 DOI: 10.1097/MOU.0b013e32835483d5]
206. Yun M, Bang SH, Kim JW, Park JY, Kim KS, Lee JD. The importance of acetyl coenzyme A synthetase for 11C-acetate uptake and cell survival in hepatocellular carcinoma. J Nucl Med 2009; 50: 1222-1228 [PMID: 19617323 DOI: 10.2967/ jnumed.109.062703]
207. Zhao Y, Butler EB, Tan M. Targeting cellular metabolism to improve cancer therapeutics. Cell Death Dis 2013; 4: e532 [PMID: 23470539 DOI: 10.1038/cddis.2013.60]
208. Liu H, Liu JY, Wu X, Zhang JT. Biochemistry, molecular biology, and pharmacology of fatty acid synthase, an emerging therapeutic target and diagnosis/prognosis marker. Int J Biochem Mol Biol 2010; 1: 69-89 [PMID: 20706604]
209. Mashima T, Seimiya H, Tsuruo T. De novo fatty-acid synthesis and related pathways as molecular targets for cancer therapy. Br J Cancer 2009; 100: 1369-1372 [PMID: 19352381 DOI: 10.1038/sj.bjc.6605007]
210. Little JL, Kridel SJ. Fatty acid synthase activity in tumor cells. Subcell Biochem 2008; 49: 169-194 [PMID: 18751912 DOI: 10.1007/978-1-4020-8831-5_7]
211. Kridel SJ, Lowther WT, Pemble CW. Fatty acid synthase inhibitors: new directions for oncology. Expert Opin Investig Drugs 2007; 16: 1817-1829 [PMID: 17970640 DOI: 10.1517/13 543784.16.11.1817]
212. Kuhajda FP. Fatty acid synthase and cancer: new application of an old pathway. Cancer Res 2006; 66: 5977-5980 [PMID: 16778164 DOI: 10.1158/0008-5472.CAN-05-4673]
213. Thupari JN, Pinn ML, Kuhajda FP. Fatty acid synthase inhibition in human breast cancer cells leads to malonyl-CoAinduced inhibition of fatty acid oxidation and cytotoxicity. Biochem Biophys Res Commun 2001; 285: 217-223 [PMID: 11444828 DOI: 10.1006/bbrc.2001.5146]
214. Li JN, Gorospe M, Chrest FJ, Kumaravel TS, Evans MK, Han WF, Pizer ES. Pharmacological inhibition of fatty acid synthase activity produces both cytostatic and cytotoxic effects modulated by p53. Cancer Res 2001; 61: 1493-1499 [PMID: 11245456]
215. Gabrielson EW, Pinn ML, Testa JR, Kuhajda FP. Increased fatty acid synthase is a therapeutic target in mesothelioma. Clin Cancer Res 2001; 7: 153-157 [PMID: 11205903]
216. Kuhajda FP, Pizer ES, Li JN, Mani NS, Frehywot GL, Townsend CA. Synthesis and antitumor activity of an inhibitor of fatty acid synthase. Proc Natl Acad Sci USA 2000; 97: 3450-3454 [PMID: 10716717 DOI: 10.1073/pnas.97.7.3450]
217. Zu XY, Zhang QH, Liu JH, Cao RX, Zhong J, Yi GH, Quan ZH, Pizzorno G. ATP citrate lyase inhibitors as novel cancer therapeutic agents. Recent Pat Anticancer Drug Discov 2012; 7: 154-167 [PMID: 22339355 DOI: 10.2174/157489212799972954]
218. Hanai J, Doro N, Sasaki AT, Kobayashi S, Cantley LC, Seth P, Sukhatme VP. Inhibition of lung cancer growth: ATP citrate lyase knockdown and statin treatment leads to dual blockade of mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K)/AKT pathways. J Cell Physiol 2012; 227: 1709-1720 [PMID: 21688263 DOI: 10.1002/ jcp.22895]
219. Wang C, Rajput S, Watabe K, Liao DF, Cao D. Acetyl-CoA carboxylase-a as a novel target for cancer therapy. Front Biosci (Schol Ed) 2010; 2: 515-526 [PMID: 20036965 DOI: 10.2741/82]
220. Zu X, Zhong J, Luo D, Tan J, Zhang Q, Wu Y, Liu J, Cao R, Wen G, Cao D. Chemical genetics of acetyl-CoA carboxylases. Molecules 2013; 18: 1704-1719 [PMID: 23358327 DOI: 10.3390/molecules18021704]
221. Poteet E, Choudhury GR, Winters A, Li W, Ryou MG, Liu R, Tang L, Ghorpade A, Wen Y, Yuan F, Keir ST, Yan H, Bigner DD, Simpkins JW, Yang SH. Reversing the Warburg effect as a treatment for glioblastoma. J Biol Chem 2013; 288: 9153-9164 [PMID: 23408428 DOI: 10.1074/jbc.M112.440354]
222. Scaglia N, Chisholm JW, Igal RA. Inhibition of stearoylCoA desaturase-1 inactivates acetyl-CoA carboxylase and impairs proliferation in cancer cells: role of AMPK. PLoS One 2009; 4: e6812 [PMID: 19710915 DOI: 10.1371/journal.pone.0006812]
223. Hess D, Chisholm JW, Igal RA. Inhibition of stearoylCoA desaturase activity blocks cell cycle progression and induces programmed cell death in lung cancer cells. PLoS One 2010; 5: e11394 [PMID: 20613975 DOI: 10.1371/journal.pone.0011394]
224. Minville-Walz M, Pierre AS, Pichon L, Bellenger S, Fèvre C, Bellenger J, Tessier C, Narce M, Rialland M. Inhibition of stearoyl-CoA desaturase 1 expression induces CHOPdependent cell death in human cancer cells. PLoS One 2010; 5: e14363 [PMID: 21179554 DOI: 10.1371/journal.pone.0014363]
225. Mason P, Liang B, Li L, Fremgen T, Murphy E, Quinn A, Madden SL, Biemann HP, Wang B, Cohen A, Komarnitsky S, Jancsics K, Hirth B, Cooper CG, Lee E, Wilson S, Krumbholz R, Schmid S, Xiang Y, Booker M, Lillie J, Carter K. SCD1 inhibition causes cancer cell death by depleting mono-unsaturated fatty acids. PLoS One 2012; 7: e33823 [PMID: 22457791 DOI: 10.1371/journal.pone.0033823]
226. Pizer ES, Pflug BR, Bova GS, Han WF, Udan MS, Nelson JB. Increased fatty acid synthase as a therapeutic target in androgen-independent prostate cancer progression. Prostate 2001; 47: 102-110 [PMID: 11340632 DOI: 10.1002/pros.1052]
227. Wang HQ, Altomare DA, Skele KL, Poulikakos PI, Kuhajda FP, Di Cristofano A, Testa JR. Positive feedback regulation between AKT activation and fatty acid synthase expression in ovarian carcinoma cells. Oncogene 2005; 24: 3574-3582 [PMID: 15806173 DOI: 10.1038/sj.onc.1208463]
228. Brusselmans K, De Schrijver E, Heyns W, Verhoeven G, Swinnen JV. Epigallocatechin-3-gallate is a potent natural inhibitor of fatty acid synthase in intact cells and selectively induces apoptosis in prostate cancer cells. Int J Cancer 2003; 106: 856-862 [PMID: 12918062 DOI: 10.1002/ijc.11317]
229. Yeh CW, Chen WJ, Chiang CT, Lin-Shiau SY, Lin JK. Suppression of fatty acid synthase in MCF-7 breast cancer cells by tea and tea polyphenols: a possible mechanism for their hypolipidemic effects. Pharmacogenomics J 2003; 3: 267-276 [PMID: 12931129]
230. Vergote D, Cren-Olivé C, Chopin V, Toillon RA, Rolando C, Hondermarck H, Le Bourhis X. (-)-Epigallocatechin (EGC) of green tea induces apoptosis of human breast cancer cells but not of their normal counterparts. Breast Cancer Res Treat 2002; 76: 195-201 [PMID: 12462380]
231. Brusselmans K, Vrolix R, Verhoeven G, Swinnen JV. Induction of cancer cell apoptosis by flavonoids is associated with their ability to inhibit fatty acid synthase activity. J Biol Chem 2005; 280: 5636-5645 [PMID: 15533929 DOI: 10.1074/jbc. M408177200]
232. Harris DM, Li L, Chen M, Lagunero FT, Go VL, Boros LG. Diverse mechanisms of growth inhibition by luteolin, resveratrol, and quercetin in MIA PaCa-2 cells: a comparative glucose tracer study with the fatty acid synthase inhibitor C75. Metabolomics 2012; 8: 201-210 [PMID: 22754424 DOI: 10.1007/s11306-011-0300-9]
233. Evans JM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD. Metformin and reduced risk of cancer in diabetic patients. BMJ 2005; 330: 1304-1305 [PMID: 15849206 DOI: 10.1136/bmj.38415.708634.F7]
234. Libby G, Donnelly LA, Donnan PT, Alessi DR, Morris AD, Evans JM. New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes. Diabetes Care 2009; 32: 1620-1625 [PMID: 19564453 DOI: 10.2337/dc08-2175]
235. Li D, Yeung SC, Hassan MM, Konopleva M, Abbruzzese JL. Antidiabetic therapies affect risk of pancreatic cancer. Gastroenterology 2009; 137: 482-488 [PMID: 19375425 DOI: 10.1053/ j.gastro.2009.04.013]
236. Ben Sahra I, Le Marchand-Brustel Y, Tanti JF, Bost F. Metformin in cancer therapy: a new perspective for an old antidiabetic drug? Mol Cancer Ther 2010; 9: 1092-1099 [PMID: 20442309 DOI: 10.1158/1535-7163.MCT-09-1186]
237. Ben Sahra I, Laurent K, Loubat A, Giorgetti-Peraldi S, Colosetti P, Auberger P, Tanti JF, Le Marchand-Brustel Y, Bost F. The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level. Oncogene 2008; 27: 3576-3586 [PMID: 18212742 DOI: 10.1038/ sj.onc.1211024]
238. Zhuang Y, Miskimins WK. Metformin induces both caspasedependent and poly(ADP-ribose) polymerase-dependent cell death in breast cancer cells. Mol Cancer Res 2011; 9: 603-615 [PMID: 21422199 DOI: 10.1158/1541-7786.MCR-10-0343]
239. Nair V, Pathi S, Jutooru I, Sreevalsan S, Basha R, Abdelrahim M, Samudio I, Safe S. Metformin inhibits pancreatic cancer cell and tumor growth and downregulates Sp transcription factors. Carcinogenesis 2013; 34: 2870-2879 [PMID: 23803693 DOI: 10.1093/carcin/bgt231]
240. Lu S, Archer MC. Sp1 coordinately regulates de novo lipogenesis and proliferation in cancer cells. Int J Cancer 2010; 126: 416-425 [PMID: 19621387 DOI: 10.1002/ijc.24761]
241. Mistafa O, Stenius U. Statins inhibit Akt/PKB signaling via P2X7 receptor in pancreatic cancer cells. Biochem Pharmacol 2009; 78: 1115-1126 [PMID: 19540829 DOI: 10.1016/ j.bcp.2009.06.016]
242. Müller C, Bockhorn AG, Klusmeier S, Kiehl M, Roeder C, Kalthoff H, Koch OM. Lovastatin inhibits proliferation of pancreatic cancer cell lines with mutant as well as with wildtype K-ras oncogene but has different effects on protein phosphorylation and induction of apoptosis. Int J Oncol 1998; 12: 717-723 [PMID: 9472115]
243. Ura H, Obara T, Nishino N, Tanno S, Okamura K, Namiki M. Cytotoxicity of simvastatin to pancreatic adenocarcinoma cells containing mutant ras gene. Jpn J Cancer Res 1994; 85: 633-638 [PMID: 8063617 DOI: 10.1111/j.1349-7006.1994.tb02406.x]
244. Liao J, Chung YT, Yang AL, Zhang M, Li H, Zhang W, Yan L, Yang GY. Atorvastatin inhibits pancreatic carcinogenesis and increases survival in LSL-KrasG12D-LSL-Trp53R172H-Pdx1-Cre mice. Mol Carcinog 2013; 52: 739-750 [PMID: 22549877 DOI: 10.1002/mc.21916]
245. Cui X, Xie Y, Chen M, Li J, Liao X, Shen J, Shi M, Li W, Zheng H, Jiang B. Statin use and risk of pancreatic cancer: a meta-analysis. Cancer Causes Control 2012; 23: 1099-1111 [PMID: 22562222 DOI: 10.1007/s10552-012-9979-9]
246. Chiu HF, Chang CC, Ho SC, Wu TN, Yang CY. Statin use and the risk of pancreatic cancer: a population-based casecontrol study. Pancreas 2011; 40: 669-672 [PMID: 21654539 DOI: 10.1097/MPA.0b013e31821fd5cd]
247. Bradley MC, Hughes CM, Cantwell MM, Murray LJ. Statins and pancreatic cancer risk: a nested case-control study. Cancer Causes Control 2010; 21: 2093-2100 [PMID: 20697797 DOI: 10.1007/s10552-010-9628-0]
248. Carey FJ, Little MW, Pugh TF, Ndokera R, Ing H, Clark A, Dennison A, Metcalfe MS, Robinson RJ, Hart AR. The differential effects of statins on the risk of developing pancreatic cancer: a case-control study in two centres in the United Kingdom. Dig Dis Sci 2013; 58: 3308-3312 [PMID: 23864194 DOI: 10.1007/s10620-013-2778-7]
249. Nakai Y, Isayama H, Sasaki T, Mizuno S, Sasahira N, Kogure H, Kawakubo K, Yamamoto N, Hirano K, Ijichi H, Tateishi K, Tada M, Koike K. Clinical outcomes of chemotherapy for diabetic and nondiabetic patients with pancreatic cancer: better prognosis with statin use in diabetic patients. Pancreas 2013; 42: 202-208 [PMID: 23000889 DOI: 10.1097/ MPA.0b013e31825de678]
250. Flavin R, Peluso S, Nguyen PL, Loda M. Fatty acid synthase as a potential therapeutic target in cancer. Future Oncol 2010; 6: 551-562 [PMID: 20373869 DOI: 10.2217/fon.10.11]
251. Migita T, Narita T, Nomura K, Miyagi E, Inazuka F, Matsuura M, Ushijima M, Mashima T, Seimiya H, Satoh Y, Okumura S, Nakagawa K, Ishikawa Y. ATP citrate lyase: activation and therapeutic implications in non-small cell lung cancer. Cancer Res 2008; 68: 8547-8554 [PMID: 18922930 DOI: 10.1158/0008-5472.CAN-08-1235]
252. Yancy HF, Mason JA, Peters S, Thompson CE, Littleton GK, Jett M, Day AA. Metastatic progression and gene expression between breast cancer cell lines from African American and Caucasian women. J Carcinog 2007; 6: 8 [PMID: 17472751 DOI: 10.1186/1477-3163-6-8]
253. Varis A, Wolf M, Monni O, Vakkari ML, Kokkola A, Moskaluk C, Frierson H, Powell SM, Knuutila S, Kallioniemi A, El-Rifai W. Targets of gene amplification and overexpression at 17q in gastric cancer. Cancer Res 2002; 62: 2625-2629 [PMID: 11980659]
254. Halliday KR, Fenoglio-Preiser C, Sillerud LO. Differentiation of human tumors from nonmalignant tissue by naturalabundance 13C NMR spectroscopy. Magn Reson Med 1988; 7: 384-411 [PMID: 2459580 DOI: 10.1002/mrm.1910070403]
255. Yahagi N, Shimano H, Hasegawa K, Ohashi K, Matsuzaka T, Najima Y, Sekiya M, Tomita S, Okazaki H, Tamura Y, Iizuka Y, Ohashi K, Nagai R, Ishibashi S, Kadowaki T, Makuuchi M, Ohnishi S, Osuga J, Yamada N. Co-ordinate activation of lipogenic enzymes in hepatocellular carcinoma. Eur J Cancer 2005; 41: 1316-1322 [PMID: 15869874 DOI: 10.1016/ j.ejca.2004.12.037]
256. Milgraum LZ, Witters LA, Pasternack GR, Kuhajda FP. Enzymes of the fatty acid synthesis pathway are highly expressed in in situ breast carcinoma. Clin Cancer Res 1997; 3: 2115-2120 [PMID: 9815604]
257. Cao Y, Pearman AT, Zimmerman GA, McIntyre TM, Prescott SM. Intracellular unesterified arachidonic acid signals apoptosis. Proc Natl Acad Sci USA 2000; 97: 11280-11285 [PMID: 11005842 DOI: 10.1073/pnas.200367597]
258. Mashima T, Sato S, Sugimoto Y, Tsuruo T, Seimiya H. Promotion of glioma cell survival by acyl-CoA synthetase 5 under extracellular acidosis conditions. Oncogene 2009; 28: 9-19 [PMID: 18806831 DOI: 10.1038/onc.2008.355]
259. Collins MA, Bednar F, Zhang Y, Brisset JC, Galbán S, Galbán CJ, Rakshit S, Flannagan KS, Adsay NV, Pasca di Magliano M. Oncogenic Kras is required for both the initiation and maintenance of pancreatic cancer in mice. J Clin Invest 2012; 122: 639-653 [PMID: 22232209 DOI: 10.1172/JCI59227]
260. Hruban RH, van Mansfeld AD, Offerhaus GJ, van Weering DH, Allison DC, Goodman SN, Kensler TW, Bose KK, Cameron JL, Bos JL. K-ras oncogene activation in adenocarcinoma of the human pancreas. A study of 82 carcinomas using a combination of mutant-enriched polymerase chain reaction analysis and allele-specific oligonucleotide hybridization. Am J Pathol 1993; 143: 545-554 [PMID: 8342602]
261. Smit VT, Boot AJ, Smits AM, Fleuren GJ, Cornelisse CJ, Bos JL. KRAS codon 12 mutations occur very frequently in pancreatic adenocarcinomas. Nucleic Acids Res 1988; 16: 7773-7782 [PMID: 3047672 DOI: 10.1093/nar/16.16.7773]
262. Cheng JQ, Ruggeri B, Klein WM, Sonoda G, Altomare DA, Watson DK, Testa JR. Amplification of AKT2 in human pancreatic cells and inhibition of AKT2 expression and tumorigenicity by antisense RNA. Proc Natl Acad Sci USA 1996; 93: 3636-3641 [PMID: 8622988]
263. Nicholson KM, Anderson NG. The protein kinase B/Akt signalling pathway in human malignancy. Cell Signal 2002; 14: 381-395 [PMID: 11882383 DOI: 10.1016/S0898-6568(01)00271-6]
264. Ruggeri BA, Huang L, Wood M, Cheng JQ, Testa JR. Amplification and overexpression of the AKT2 oncogene in a subset of human pancreatic ductal adenocarcinomas. Mol Carcinog 1998; 21: 81-86 [PMID: 9496907 DOI: 10.1002/(SICI) 1098-2744(199802)]
265. Aumayr K, Soleiman A, Sahora K, Schindl M, Werba G, Schoppmann SF, Birner P. HER2 Gene Amplification and Protein Expression in Pancreatic Ductal Adenocarcinomas. Appl Immunohistochem Mol Morphol 2014; 22: 146-152 [PMID: 23702645 DOI: 10.1097/PAI.0b013e31828dc392]
266. Chou A, Waddell N, Cowley MJ, Gill AJ, Chang DK, Patch AM, Nones K, Wu J, Pinese M, Johns AL, Miller DK, Kassahn KS, Nagrial AM, Wasan H, Goldstein D, Toon CW, Chin V, Chantrill L, Humphris J, Mead RS, Rooman I, Samra JS, Pajic M, Musgrove EA, Pearson JV, Morey AL, Grimmond SM, Biankin AV. Clinical and molecular characteriza-tion of HER2 amplified-pancreatic cancer. Genome Med 2013; 5: 78 [PMID: 24004612 DOI: 10.1186/gm482]
267. Walsh N, Kennedy S, Larkin A, Corkery B, O'Driscoll L, Clynes M, Crown J, O'Donovan N. EGFR and HER2 inhibition in pancreatic cancer. Invest New Drugs 2013; 31: 558-566 [PMID: 23076814 DOI: 10.1007/s10637-012-9891-x]
268. Yamanaka Y, Friess H, Kobrin MS, Büchler M, Kunz J, Beger HG, Korc M. Overexpression of HER2/neu oncogene in human pancreatic carcinoma. Hum Pathol 1993; 24: 1127-1134 [PMID: 8104858 DOI: 10.1016/0046-8177(93)90194-L]
269. Dang CV, Le A, Gao P. MYC-induced cancer cell energy metabolism and therapeutic opportunities. Clin Cancer Res 2009; 15: 6479-6483 [PMID: 19861459 DOI: 10.1158/1078-0432. CCR-09-0889]
270. Oren M. Decision making by p53: life, death and cancer. Cell Death Differ 2003; 10: 431-442 [PMID: 12719720 DOI: 10.1038/ sj.cdd.4401183]
271. Redston MS, Caldas C, Seymour AB, Hruban RH, da Costa L, Yeo CJ, Kern SE. p53 mutations in pancreatic carcinoma and evidence of common involvement of homocopolymer tracts in DNA microdeletions. Cancer Res 1994; 54: 3025-3033 [PMID: 8187092]
272. Scarpa A, Capelli P, Mukai K, Zamboni G, Oda T, Iacono C, Hirohashi S. Pancreatic adenocarcinomas frequently show p53 gene mutations. Am J Pathol 1993; 142: 1534-1543 [PMID: 8494051]
273. Shen L, Sun X, Fu Z, Yang G, Li J, Yao L. The fundamental role of the p53 pathway in tumor metabolism and its implication in tumor therapy. Clin Cancer Res 2012; 18: 1561-1567 [PMID: 22307140 DOI: 10.1158/1078-0432.CCR-11-3040]
274. Hahn SA, Schutte M, Hoque AT, Moskaluk CA, da Costa LT, Rozenblum E, Weinstein CL, Fischer A, Yeo CJ, Hruban RH, Kern SE. DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. Science 1996; 271: 350-353 [PMID: 8553070 DOI: 10.1126/science.271.5247.350]
275. Iacobuzio-Donahue CA, Song J, Parmiagiani G, Yeo CJ, Hruban RH, Kern SE. Missense mutations of MADH4: characterization of the mutational hot spot and functional consequences in human tumors. Clin Cancer Res 2004; 10: 1597-1604 [PMID: 15014009 DOI: 10.1158/1078-0432. CCR-1121-3]
276. Liu F. SMAD4/DPC4 and pancreatic cancer survival. Commentary re: M. Tascilar et al., The SMAD4 protein and prognosis of pancreatic ductal adenocarcinoma. Clin. Cancer Res., 7: 4115-4121, 2001. Clin Cancer Res 2001; 7: 3853-3856 [PMID: 11751474]
277. Katajisto P, Vallenius T, Vaahtomeri K, Ekman N, Udd L, Tiainen M, Mäkelä TP. The LKB1 tumor suppressor kinase in human disease. Biochim Biophys Acta 2007; 1775: 63-75 [PMID: 17010524 DOI: 10.1016/j.bbcan.2006.08.003]
278. Sato N, Rosty C, Jansen M, Fukushima N, Ueki T, Yeo CJ, Cameron JL, Iacobuzio-Donahue CA, Hruban RH, Goggins M. STK11/LKB1 Peutz-Jeghers gene inactivation in intraductal papillary-mucinous neoplasms of the pancreas. Am J Pathol 2001; 159: 2017-2022 [PMID: 11733352 DOI: 10.1016/ S0002-9440(10)63053-2]
279. Su GH, Hruban RH, Bansal RK, Bova GS, Tang DJ, Shekher MC, Westerman AM, Entius MM, Goggins M, Yeo CJ, Kern SE. Germline and somatic mutations of the STK11/LKB1 Peutz-Jeghers gene in pancreatic and biliary cancers. Am J Pathol 1999; 154: 1835-1840 [PMID: 10362809 DOI: 10.1016/ S0002-9440(10)65440-5]
280. Caldas C, Hahn SA, da Costa LT, Redston MS, Schutte M, Seymour AB, Weinstein CL, Hruban RH, Yeo CJ, Kern SE. Frequent somatic mutations and homozygous deletions of the p16 (MTS1) gene in pancreatic adenocarcinoma. Nat Genet 1994; 8: 27-32 [PMID: 7726912 DOI: 10.1038/ng0994-27]
281. Schutte M, Hruban RH, Geradts J, Maynard R, Hilgers W, Rabindran SK, Moskaluk CA, Hahn SA, Schwarte-Waldhoff I, Schmiegel W, Baylin SB, Kern SE, Herman JG. Abrogation of the Rb/p16 tumor-suppressive pathway in virtually all pancreatic carcinomas. Cancer Res 1997; 57: 3126-3130 [PMID: 9242437]
282. Ueki T, Toyota M, Sohn T, Yeo CJ, Issa JP, Hruban RH, Goggins M. Hypermethylation of multiple genes in pancreatic adenocarcinoma. Cancer Res 2000; 60: 1835-1839 [PMID: 10766168]
283. Okami K, Wu L, Riggins G, Cairns P, Goggins M, Evron E, Halachmi N, Ahrendt SA, Reed AL, Hilgers W, Kern SE, Koch WM, Sidransky D, Jen J. Analysis of PTEN/MMAC1 alterations in aerodigestive tract tumors. Cancer Res 1998; 58: 509-511 [PMID: 9458098]
284. Ying H, Elpek KG, Vinjamoori A, Zimmerman SM, Chu GC, Yan H, Fletcher-Sananikone E, Zhang H, Liu Y, Wang W, Ren X, Zheng H, Kimmelman AC, Paik JH, Lim C, Perry SR, Jiang S, Malinn B, Protopopov A, Colla S, Xiao Y, Hezel AF, Bardeesy N, Turley SJ, Wang YA, Chin L, Thayer SP, De-Pinho RA. PTEN is a major tumor suppressor in pancreatic ductal adenocarcinoma and regulates an NF-κB-cytokine network. Cancer Discov 2011; 1: 158-169 [PMID: 21984975 DOI: 10.1158/2159-8290.CD-11-0031]
285. Hong SM, Park JY, Hruban RH, Goggins M. Molecular signatures of pancreatic cancer. Arch Pathol Lab Med 2011; 135: 716-727 [PMID: 21631264 DOI: 10.1043/2010-0566-RA.1]
286. Iacobuzio-Donahue CA, Velculescu VE, Wolfgang CL, Hruban RH. Genetic basis of pancreas cancer development and progression: insights from whole-exome and whole-genome sequencing. Clin Cancer Res 2012; 18: 4257-4265 [PMID: 22896692 DOI: 10.1158/1078-0432.CCR-12-0315]
287. Schleger C, Verbeke C, Hildenbrand R, Zentgraf H, Bleyl U. c-MYC activation in primary and metastatic ductal adenocarcinoma of the pancreas: incidence, mechanisms, and clinical significance. Mod Pathol 2002; 15: 462-469 [PMID: 11950922]
288. Abraham SC, Wu TT, Hruban RH, Lee JH, Yeo CJ, Conlon K, Brennan M, Cameron JL, Klimstra DS. Genetic and immunohistochemical analysis of pancreatic acinar cell carcinoma: frequent allelic loss on chromosome 11p and alterations in the APC/beta-catenin pathway. Am J Pathol 2002; 160: 953-962 [PMID: 11891193 DOI: 10.1016/ S0002-9440(10)64917-6]
289. Hosoda W, Sasaki E, Murakami Y, Yamao K, Shimizu Y, Yatabe Y. BCL10 as a useful marker for pancreatic acinar cell carcinoma, especially using endoscopic ultrasound cytology specimens. Pathol Int 2013; 63: 176-182 [PMID: 23530562 DOI: 10.1111/pin.12045]
290. Skoulidis F, Cassidy LD, Pisupati V, Jonasson JG, Bjarnason H, Eyfjord JE, Karreth FA, Lim M, Barber LM, Clatworthy SA, Davies SE, Olive KP, Tuveson DA, Venkitaraman AR. Germline Brca2 heterozygosity promotes Kras(G12D)-driven carcinogenesis in a murine model of familial pancreatic cancer. Cancer Cell 2010; 18: 499-509 [PMID: 21056012 DOI: 10.1016/j.ccr.2010.10.015]
291. Brody JR, Costantino CL, Potoczek M, Cozzitorto J, McCue P, Yeo CJ, Hruban RH, Witkiewicz AK. Adenosquamous carcinoma of the pancreas harbors KRAS2, DPC4 and TP53 molecular alterations similar to pancreatic ductal adenocarcinoma. Mod Pathol 2009; 22: 651-659 [PMID: 19270646 DOI: 10.1038/modpathol.2009]
292. Trikudanathan G, Dasanu CA. Adenosquamous carcinoma of the pancreas: a distinct clinicopathologic entity. South Med J 2010; 103: 903-910 [PMID: 20697320 DOI: 10.1097/ SMJ.0b013e3181ebadbd]
293. Nissim S, Idos GE, Wu B. Genetic markers of malignant transformation in intraductal papillary mucinous neoplasm of the pancreas: a meta-analysis. Pancreas 2012; 41: 1195-1205 [PMID: 22750975 DOI: 10.1097/MPA.0b013e3182580fb4]
294. Wu J, Matthaei H, Maitra A, Dal Molin M, Wood LD, Eshleman JR, Goggins M, Canto MI, Schulick RD, Edil BH, Wolfgang CL, Klein AP, Diaz LA, Allen PJ, Schmidt CM, Kinzler KW, Papadopoulos N, Hruban RH, Vogelstein B. Recurrent GNAS mutations define an unexpected pathway for pancreatic cyst development. Sci Transl Med 2011; 3: 92ra66 [PMID: 21775669 DOI: 10.1126/scitranslmed.3002543]
295. Fukushima N, Fukayama M. Mucinous cystic neoplasms of the pancreas: pathology and molecular genetics. J Hepatobiliary Pancreat Surg 2007; 14: 238-242 [PMID: 17520198]
296. Kosmahl M, Wagner J, Peters K, Sipos B, Klöppel G. Serous cystic neoplasms of the pancreas: an immunohistochemical analysis revealing alpha-inhibin, neuron-specific enolase, and MUC6 as new markers. Am J Surg Pathol 2004; 28: 339-346 [PMID: 15104296]
297. Kobayashi T, Ozasa M, Miyashita K, Saga A, Miwa K, Saito M, Morioka M, Takeuchi M, Takenouchi N, Yabiku T, Kanno H, Yuzawa S, Tanino M, Tanaka S, Kawakami H, Asaka M, Sakamoto N. Large solid-pseudopapillary neoplasm of the pancreas with aberrant protein expression and mutation of β-catenin: a case report and literature review of the distribution of β-catenin mutation. Intern Med 2013; 52: 2051-2056 [PMID: 24042511 DOI: 10.2169/internalmedicine.52.9512]
298. Vassos N, Agaimy A, Klein P, Hohenberger W, Croner RS. Solid-pseudopapillary neoplasm (SPN) of the pancreas: case series and literature review on an enigmatic entity. Int J Clin Exp Pathol 2013; 6: 1051-1059 [PMID: 23696922]
299. Weisbrod AB, Zhang L, Jain M, Barak S, Quezado MM, Kebebew E. Altered PTEN, ATRX, CHGA, CHGB, and TP53 expression are associated with aggressive VHL-associated pancreatic neuroendocrine tumors. Horm Cancer 2013; 4: 165-175 [PMID: 23361940 DOI: 10.1007/s12672-013-0134-1]
300. Zhang J, Francois R, Iyer R, Seshadri M, Zajac-Kaye M, Hochwald SN. Current understanding of the molecular biology of pancreatic neuroendocrine tumors. J Natl Cancer Inst 2013; 105: 1005-1017 [PMID: 23840053 DOI: 10.1093/jnci/djt135]
301. Heaphy CM, de Wilde RF, Jiao Y, Klein AP, Edil BH, Shi C, Bettegowda C, Rodriguez FJ, Eberhart CG, Hebbar S, Offerhaus GJ, McLendon R, Rasheed BA, He Y, Yan H, Bigner DD, Oba-Shinjo SM, Marie SK, Riggins GJ, Kinzler KW, Vogelstein B, Hruban RH, Maitra A, Papadopoulos N, Meeker AK. Altered telomeres in tumors with ATRX and DAXX mutations. Science 2011; 333: 425 [PMID: 21719641 DOI: 10.1126/ science.1207313]
302. Jiao Y, Shi C, Edil BH, de Wilde RF, Klimstra DS, Maitra A, Schulick RD, Tang LH, Wolfgang CL, Choti MA, Velculescu VE, Diaz LA, Vogelstein B, Kinzler KW, Hruban RH, Papadopoulos N. DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors. Science 2011; 331: 1199-1203 [PMID: 21252315 DOI: 10.1126/science.1200609]
303. Pizer ES, Jackisch C, Wood FD, Pasternack GR, Davidson NE, Kuhajda FP. Inhibition of fatty acid synthesis induces programmed cell death in human breast cancer cells. Cancer Res 1996; 56: 2745-2747 [PMID: 8665507]
304. Pizer ES, Wood FD, Heine HS, Romantsev FE, Pasternack GR, Kuhajda FP. Inhibition of fatty acid synthesis delays disease progression in a xenograft model of ovarian cancer. Cancer Res 1996; 56: 1189-1193 [PMID: 8640795]
305. Orita H, Coulter J, Lemmon C, Tully E, Vadlamudi A, Medghalchi SM, Kuhajda FP, Gabrielson E. Selective inhibition of fatty acid synthase for lung cancer treatment. Clin Cancer Res 2007; 13: 7139-7145 [PMID: 18056164 DOI: 10.1158/1078-0432.CCR-07-1186]
306. Zhou W, Han WF, Landree LE, Thupari JN, Pinn ML, Bililign T, Kim EK, Vadlamudi A, Medghalchi SM, El Meskini R, Ronnett GV, Townsend CA, Kuhajda FP. Fatty acid synthase inhibition activates AMP-activated protein kinase in SKOV3 human ovarian cancer cells. Cancer Res 2007; 67: 2964-2971 [PMID: 17409402 DOI: 10.1158/0008-5472.CAN-06-3439]
307. Kridel SJ, Axelrod F, Rozenkrantz N, Smith JW. Orlistat is a novel inhibitor of fatty acid synthase with antitumor activity. Cancer Res 2004; 64: 2070-2075 [PMID: 15026345 DOI: 10.1158/0008-5472.CAN-03-3645]
308. Hatzivassiliou G, Zhao F, Bauer DE, Andreadis C, Shaw AN, Dhanak D, Hingorani SR, Tuveson DA, Thompson CB. ATP citrate lyase inhibition can suppress tumor cell growth. Cancer Cell 2005; 8: 311-321 [PMID: 16226706 DOI: 10.1016/ j.ccr.2005.09.008]
309. Beckers A, Organe S, Timmermans L, Scheys K, Peeters A, Brusselmans K, Verhoeven G, Swinnen JV. Chemical inhibition of acetyl-CoA carboxylase induces growth arrest and cytotoxicity selectively in cancer cells. Cancer Res 2007; 67: 8180-8187 [PMID: 17804731 DOI: 10.1158/0008-5472. CAN-07-0389]
310. Wang C, Xu C, Sun M, Luo D, Liao DF, Cao D. Acetyl-CoA carboxylase-alpha inhibitor TOFA induces human cancer cell apoptosis. Biochem Biophys Res Commun 2009; 385: 302-306 [PMID: 19450551 DOI: 10.1016/j.bbrc.2009.05.045]
311. Mashima T, Oh-hara T, Sato S, Mochizuki M, Sugimoto Y, Yamazaki K, Hamada J, Tada M, Moriuchi T, Ishikawa Y, Kato Y, Tomoda H, Yamori T, Tsuruo T. p53-defective tumors with a functional apoptosome-mediated pathway: a new therapeutic target. J Natl Cancer Inst 2005; 97: 765-777 [PMID: 15900046 DOI: 10.1093/jnci/dji133]