Tumor cell metabolism: An integral view

Cancer Biology and Therapy

Volumn 12, Issue 11, 2011, Pages 939-948

  Romero Garcia, Susana ^a   Lopez Gonzalez, Jose Sullivan ^a   Báez Viveros, José Luis ^b   Aguilar Cazares, Dolores ^a   Prado Garcia, Heriberto ^a  

^a INSTITUTO NACIONAL DE ENFERMEDADES RESPIRATORIAS   (Mexico)

^b UNIVERSIDAD AUTÓNOMA DEL ESTADO DE MORELOS   (Mexico)

Author keywords

Cancer; Glutamine; Glycolysis; Hypoxia; Lactic acidosis; Metabolic reprogramming; Tumor cell mitochondria

Indexed keywords

ACETYL COENZYME A CARBOXYLASE; ADENOSINE TRIPHOSPHATE; ADENOSINE TRIPHOSPHATE CITRATE LYASE; DNA; FATTY ACID SYNTHASE; GLUCOSE; GLUCOSE TRANSPORTER 1; GLUCOSE TRANSPORTER 3; GLUTAMINE; HYPOXIA INDUCIBLE FACTOR 1BETA; LACTATE DEHYDROGENASE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; TRANSKETOLASE;

BREAST CANCER; CARBON NUCLEAR MAGNETIC RESONANCE; CELL METABOLISM; CELL PROLIFERATION; CITRIC ACID CYCLE; DNA DAMAGE; DNA REPAIR; DNA SYNTHESIS; GLYCOLYSIS; HUMAN; HYPOXIA; LACTIC ACIDOSIS; LIVER CELL CARCINOMA; LYMPHATIC LEUKEMIA; NEUROENDOCRINE TUMOR; NONHUMAN; NUCLEAR REPROGRAMMING; OXIDATIVE PHOSPHORYLATION; PROTEIN EXPRESSION; REVIEW; TUMOR CELL; TUMOR METABOLISM; TUMOR MICROENVIRONMENT;

ACIDOSIS; AEROBIOSIS; ANIMALS; CELL HYPOXIA; CELL PROLIFERATION; GLUTAMINE; GLYCOLYSIS; HUMANS; LIPID METABOLISM; NEOPLASMS; NUCLEOTIDES;

EID: 82755195292     PISSN: 15384047     EISSN: 15558576     Source Type: Journal    
DOI: 10.4161/cbt.12.11.18140     Document Type: Review

References (105)

1. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000; 100:57-70; PMID:10647931; http://dx.doi.org/10.1016/S0092-8674(00)81683-9
2. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144:646-74; PMID: 21376230; http://dx.doi.org/10.1016/j.cell.2011.02.013
3. Gillies RJ, Robey I, Gatenby RA. Causes and consequences of increased glucose metabolism of cancers. J Nucl Med 2008; 49:24S-42S; PMID:18523064; http://dx.doi.org/10.2967/jnumed.107.047258
4. Kroemer G, Pouyssegur J. Tumor cell metabolism: cancer's Achilles' heel. Cancer Cell 2008; 13:472-82; PMID:18538731; http://dx.doi.org/10.1016/j.ccr. 2008.05.005
5. Ortega AD, Sánchez-Aragó M, Giner-Sánchez D, Sánchez-Cenizo L, Willers I, Cuezva JM. Glucose avidity of carcinomas. Cancer Lett 2009; 276:125-35; PMID:18790562; http://dx.doi.org/10.1016/j.canlet. 2008.08.007
6. 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; http://dx.doi.org/10.1016/ j.cmet.2007.10.002
7. Warburg O. On the origin of cancer cells. Science 1956; 123:309-14; PMID:13298683; http://dx.doi.org/10.1126/science.123.3191.309
8. Vogelstein B, Kinzler KW. Cancer genes and the pathways they control. Nat Med 2004; 10:789-99; PMID:15286780; http://dx.doi.org/10.1038/nm1087
9. Moreno-Sánchez R, Rodríguez-Enríquez S, Marín-Hernández A, Saavedra E. Energy metabolism in tumor cells. FEBS J 2007; 274:1393-418; PMID: 17302740; http://dx.doi.org/10.1111/j.1742- 4658.2007.05686.x
10. Kolev Y, Uetake H, Takagi Y, Sugihara K. Lactate dehydrogenase-5 (LDH-5) expression in human gastric cancer: association with hypoxia-inducible factor (HIF-1alpha) pathway, angiogenic factors production and poor prognosis. Ann Surg Oncol 2008; 15:2336-44; PMID:18521687; http://dx.doi.org/10.1245/s10434-008- 9955-5
11. Koukourakis MI, Giatromanolaki A, Winter S, Leek R, Sivridis E, Harris AL. Lactate dehydrogenase 5 expression in squamous cell head and neck cancer relates to prognosis following radical or postoperative radiotherapy. Oncology 2009; 77:285-92; PMID:19923867; http://dx.doi.org/10.1159/000259260
12. Kayser G, Kassem A, Sienel W, Schulte-Uentrop L, Mattern D, et al. Lactate-dehydrogenase 5 is overexpressed in non-small cell lung cancer and correlates with the expression of the transketolase-like protein 1. Diagn Pathol 2010; 5:1-10; PMID:20205795; http://dx.doi.org/10.1186/1746-1596-5-1
13. Fantin VR, St-Pierre J, Leder P. Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer Cell 2006; 9:425-34; PMID:16766262; http://dx.doi.org/10.1016/j.ccr.2006. 04.023
14. Gottlieb E, Tomlinson IP. Mitochondrial tumour suppressors: a genetic and biochemical update. Nat Rev Cancer 2005; 5:857-66; PMID:16327764; http://dx.doi.org/10.1038/nrc1737
15. Robey RB, Hay N. Is Akt the "Warburg kinase"? Akt-energy metabolism interactions and oncogenesis. Semin Cancer Biol 2009; 19:25-31; PMID:19130886; http://dx.doi.org/10.1016/j.semcancer.2008.11.010
16. Altenberg B, Greulich KO. Genes of glycolysis are ubiquitously overexpressed in 24 cancer classes. Genomics 2004; 84:1014-20; PMID:15533718; http://dx.doi.org/10.1016/j.ygeno.2004.08.010
17. Lu Y, Yi Y, Liu P, Wen W, James M, Wang D, et al. Common human cancer genes discovered by integrated gene-expression analysis. PLoS ONE 2007; 2:e1149; PMID:17989776; http://dx.doi.org/10.1371/journal.pone.0001149
18. Amann T, Maegdefrau U, Hartmann A, Agaimy A, Marienhagen J, Weiss TS, et al. GLUT1 expression is increased in hepatocellular carcinoma and promotes tumorigenesis. Am J Pathol 2009; 174:1544-52; PMID:19286567; http://dx.doi.org/10.2353/ajpath.2009.080596
19. Meadows AL, Kong B, Berdichevsky M, Roy S, Rosiva R, Blanch HW, et al. Metabolic and morphological differences between rapidly proliferating cancerous and normal breast epithelial cells. Biotechnol Prog 2008; 24:334-41; PMID:18307352; http://dx.doi.org/10.1021/bp070301d
20. Ozbudak IH, Shilo K, Tavora F, Rassaei N, Chu WS, Fukuoka J, et al. Glucose transporter-1 in pulmonary neuroendocrine carcinomas: expression and survival analysis. Mod Pathol 2009; 22:633-8; PMID:19234439; http://dx.doi.org/10.1038/modpathol.2009.6
21. Boag JM, Beesley AH, Firth MJ, Freitas JR, Ford J, Hoffmann K, et al. Altered glucose metabolism in childhood pre-B acute lymphoblastic leukaemia. Leukemia 2006; 20:1731-7; PMID:17041637; http://dx.doi.org/10.1038/sj.leu. 2404365
22. DeBerardinis RJ, Mancuso A, Daikhin E, Nissim I, Yudkoff M, Wehrli S, et al. 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; 104:19345-50; PMID:18032601; http://dx.doi.org/10. 1073/pnas. 0709747104
23. Yalcin A, Telang S, Clem B, Chesney J. Regulation of glucose metabolism by 6-phosphofructo-2-kinase/fructose- 2,6-bisphosphatases in cancer. Exp Mol Pathol 2009; 86:174-9; PMID:19454274; http://dx.doi.org/10.1016/j.yexmp.2009.01. 003
24. Matheson BK, Adams JL, Zou J, Patel R, Franklin RB. Effect of metabolic inhibitors on ATP and citrate content in PC3 prostate cancer cells. Prostate 2007;67:1211-8; PMID:17525933; http://dx.doi.org/10. 1002/pros.20617
25. Wang W, Fridman A, Blackledge W, Connelly S, Wilson IA, Pilz RB, et al. The phosphatidylinositol 3-kinase/akt cassette regulates purine nucleotide synthesis. J Biol Chem 2009; 284:3521-8; PMID:19068483; http://dx.doi.org/10. 1074/jbc.M806707200
26. Chen JL, Lucas JE, Schroeder T, Mori S, Wu J, Nevins J, et al. The genomic analysis of lactic acidosis and acidosis response in human cancers. PLoS Genet 2008; 4:e1000293; PMID:19057672; http://dx.doi.org/10.1371/journal.pgen. 1000293
27. Laconi E. The evolving concept of tumor microenvironments. Bioessays 2007; 29:738-44; PMID: 17621638; http://dx.doi.org/10.1002/bies.20606
28. Gort EH, Groot AJ, van der Wall E, van Diest PJ, Vooijs MA. Hypoxic regulation of metastasis via hypoxia-inducible factors. Curr Mol Med 2008; 8: 60-7; PMID:18289014; http://dx.doi.org/10.2174/156652408783565568
29. Semenza GL. Tumor metabolism: cancer cells give and take lactate. J Clin Invest 2008; 118:3835-7; PMID: 19033652
30. Heddleston JM, Li Z, Lathia JD, Bao S, Hjelmeland AB, Rich JN. Hypoxia inducible factors in cancer stem cells. Br J Cancer 2010; 102:789-95; PMID:20104230; http://dx.doi.org/10.1038/sj.bjc.6605551
31. Sonveaux P, Végran F, Schroeder T, Wergin MC, Verrax J, Rabbani ZN, et al. Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice. J Clin Invest 2008; 118:3930-42; PMID:19033663
32. Weinmann M, Jendrossek V, Güner D, Goecke B, Belka C. Cyclic exposure to hypoxia and reoxygenation selects for tumor cells with defects in mitochondrial apoptotic pathways. FASEB J 2004; 18:1906-8; PMID: 15456741
33. Marín-Hernández A, Gallardo-Pérez JC, Ralph SJ, Rodríguez-Enríquez S, Moreno-Sánchez R. HIF-1alpha modulates energy metabolism in cancer cells by inducing over-expression of specific glycolytic isoforms. Mini Rev Med Chem 2009; 9:1084-101; PMID:19689405; http://dx.doi.org/10.2174/138955709788922610
34. Zancan P, Sola-Penna M, Furtado CM, Da Silva D. Differential expression of phosphofructokinase-1 isoforms correlates with the glycolytic efficiency of breast cancer cells. Mol Genet Metab 2010; 100:372-8; PMID:20483646; http://dx.doi.org/10.1016/j.ymgme. 2010.04.006
35. Ao A, Wang H, Kamarajugadda S, Lu J. Involvement of estrogen-related receptors in transcriptional response to hypoxia and growth of solid tumors. Proc Natl Acad Sci USA 2008; 105:7821-6; PMID:18509053; http://dx.doi.org/10. 1073/pnas.0711677105
36. Korotchkina LG, Patel MS. Site specificity of four pyruvate dehydrogenase kinase isoenzymes toward the three phosphorylation sites of human pyruvate dehydrogenase. J Biol Chem 2001; 276:37223-9; PMID: 11486000; http://dx.doi.org/10.1074/jbc.M103069200
37. Korotchkina LG, Sidhu S, Patel MS. Characterization of testis-specific isoenzyme of human pyruvate dehydrogenase. J Biol Chem 2006; 281:9688-96; PMID: 16436377; http://dx.doi.org/10.1074/jbc.M511481200
38. Bartrons R, Caro J. Hypoxia, glucose metabolism and the Warburg's effect. J Bioenerg Biomembr 2007; 39: 223-9; PMID:17661163; http://dx.doi.org/10.1007/ s10863-007-9080-3
39. Rankin EB, Giaccia AJ. The role of hypoxia-inducible factors in tumorigenesis. Cell Death Differ 2008; 15:678-85; PMID:18259193; http://dx.doi.org/10.1038/cdd.2008.21
40. Denko NC. Hypoxia, HIF1 and glucose metabolism in the solid tumour. Nat Rev Cancer 2008; 8:705-13; PMID:19143055; http://dx.doi.org/10.1038/nrc2468
41. Boulahbel H, Durán RV, Gottlieb E. Prolyl hydroxylases as regulators of cell metabolism. Biochem Soc Trans 2009; 37:291-4; PMID:19143649; http://dx.doi.org/10.1042/BST0370291
42. Maynard MA, Ohh M. The role of hypoxia-inducible factors in cancer. Cell Mol Life Sci 2007; 64:2170-80; PMID:17514355; http://dx.doi.org/10.1007/s00018- 007-7082-2
43. Koivunen P, Hirsilä M, Remes AM, Hassinen IE, Kivirikko KI, Myllyharju J. Inhibition of hypoxia-inducible factor (HIF) hydroxylases by citric acid cycle intermediates: possible links between cell metabolism and stabilization of HIF. J Biol Chem 2007; 282:4524-32; PMID:17182618; http://dx.doi.org/10.1074/jbc. M610415200
44. Pollard PJ, Brière JJ, Alam NA, Barwell J, Barclay E, Wortham NC, et al. Accumulation of Krebs cycle intermediates and over-expression of HIF1alpha in tumours which result from germline FH and SDH mutations. Hum Mol Genet 2005; 14:2231-9; PMID: 15987702; http://dx.doi.org/10.1093/hmg/ddi227
45. Dalgard CL, Lu H, Mohyeldin A, Verma A. Endogenous 2-oxoacids differentially regulate expression of oxygen sensors. Biochem J 2004; 380:419-24; PMID:14984367; http://dx.doi.org/10.1042/ BJ20031647
46. Luo W, Hu H, Chang R, Zhong J, Knabel M, O'Meally R, et al. Pyruvate kinase M2 is a PHD3- stimulated coactivator for hypoxia-inducible factor 1. Cell 2011; 145:732-44; PMID:21620138; http://dx.doi.org/10.1016/j.cell.2011.03.054
47. Airley RE, Mobasheri A. Hypoxic regulation of glucose transport, anaerobic metabolism and angiogenesis in cancer: novel pathways and targets for anticancer therapeutics. Chemotherapy 2007; 53:233-56; PMID: 17595539; http://dx.doi.org/10.1159/000104457
48. Hunter A, Hendrikse A, Renan M, Abratt R. Does the tumor microenvironment influence radiation-induced apoptosis? Apoptosis 2006; 11:1727-35; PMID: 16927015; http://dx.doi.org/10.1007/s10495-006-9789-1
49. Moellering RE, Black KC, Krishnamurty C, Baggett BK, Stafford P, Rain M, et al. Acid treatment of melanoma cells selects for invasive phenotypes. Clin Exp Metastasis 2008; 25:411-25; PMID:18301995; http://dx.doi.org/10.1007/s10585- 008-9145-7
50. Mekhail K, Rivero-Lopez L, Khacho M, Lee S. Restriction of rRNA synthesis by VHL maintains energy equilibrium under hypoxia. Cell Cycle 2006; 5:2401- 13; PMID:17102617; http://dx.doi.org/10.4161/cc.5.20.3387
51. Chen JL, Merl D, Peterson CW, Wu J, Liu PY, Yin H, et al. Lactic acidosis triggers starvation response with paradoxical induction of TXNIP through MondoA. PLoS Genet 2010; 6:e1001093; PMID:20844768; http://dx.doi.org/10.1371/ journal.pgen.1001093
52. Smallbone K, Gatenby RA, Gillies RJ, Maini PK, Gavaghan DJ. Metabolic changes during carcinogenesis: potential impact on invasiveness. J Theor Biol 2007; 244:703-13; PMID:17055536; http://dx.doi. org/10.1016/j.jtbi.2006.09.010
53. Chiche J, Brahimi-Horn MC, Pouysségur J. Tumour hypoxia induces a metabolic shift causing acidosis: a common feature in cancer. J Cell Mol Med 2010; 14:771-94; PMID:20015196; http://dx.doi.org/10. 1111/j.1582-4934.2009. 00994.x
54. Ihnatko R, Kubes M, Takacova M, Sedlakova O, Sedlak J, Pastorek J, et al. Extracellular acidosis elevates carbonic anhydrase IX in human glioblastoma cells via transcriptional modulation that does not depend on hypoxia. Int J Oncol 2006; 29:1025-33; PMID: 16964400
55. Chiche J, Ilc K, Laferrière J, Trottier E, Dayan F, Mazure NM, et al. Hypoxia-inducible carbonic anhydrase IX and XII promote tumor cell growth by counteracting acidosis through the regulation of the intracellular pH. Cancer Res 2009; 69:358-68; PMID: 19118021; http://dx.doi.org/10.1158/0008-5472.CAN-08- 2470
56. Mekhail K, Gunaratnam L, Bonicalzi ME, Lee S. HIF activation by pH-dependent nucleolar sequestration of VHL. Nat Cell Biol 2004; 6:642-7; PMID:15181450; http://dx.doi.org/10.1038/ncb1144
57. Willam C, Warnecke C, Schefold JC, Kügler J, Koehne P, Frei U, et al. Inconsistent effects of acidosis on HIF-alpha protein and its target genes. Pflugers Arch 2006; 451:534-43; PMID:16208522; http://dx.doi.org/10.1007/s00424- 005-1486-3
58. Martínez D, Vermeulen M, Trevani A, Ceballos A, Sabatté J, Gamberale R, et al. Extracellular acidosis induces neutrophil activation by a mechanism dependent on activation of phosphatidylinositol 3-kinase/Akt and ERK pathways. J Immunol 2006; 176:1163-71; PMID:16394005
59. Dang CV. Rethinking the Warburg effect with Myc micromanaging glutamine metabolism. Cancer Res 2010; 70:859-62; PMID:20086171; http://dx.doi.org/10. 1158/0008-5472.CAN-09-3556
60. Medina MA. Glutamine and cancer. J Nutr 2001;131:2539S-42S; PMID:11533309
61. Szeliga M, Obara-Michlewska M. Glutamine in neoplastic cells: focus on the expression and roles of glutaminases. Neurochem Int 2009; 55:71-5; PMID: 19428809; http://dx.doi.org/10.1016/j.neuint.2009.01.008
62. Tong X, Zhao F, Thompson CB. The molecular determinants of de novo nucleotide biosynthesis in cancer cells. Curr Opin Genet Dev 2009; 19:32-7; PMID:19201187; http://dx.doi.org/10.1016/j.gde.2009.01.002
63. Matés JM, Segura JA, Campos-Sandoval JA, Lobo C, Alonso L, Alonso FJ, et al. Glutamine homeostasis and mitochondrial dynamics. Int J Biochem Cell Biol 2009; 41:2051-61; PMID:19703661; http://dx.doi.org/10.1016/j.biocel.2009. 03.003
64. McGivan JD, Bungard CI. The transport of glutamine into mammalian cells. Front Biosci 2007; 12:874-82; PMID:17127344; http://dx.doi.org/10.2741/2109
65. Gallagher FA, Kettunen MI, Day SE, Lerche M, Brindle KM. 13C MR spectroscopy measurements of glutaminase activity in human hepatocellular carcinoma cells using hyperpolarized 13C-labeled glutamine. Magn Reson Med 2008; 60:253-7; PMID:18666104; http://dx.doi.org/10.1002/mrm.21650
66. Brand A, Engelmann J, Leibfritz D. A 13C NMR study on fluxes into the TCA cycle of neuronal and glial tumor cell lines and primary cells. Biochimie 1992; 74:941-8; PMID:1334702; http://dx.doi.org/10.1016/0300-9084(92)90078-S
67. Liu KJ, Kleps R, Henderson T, Nyhus L. 13C NMR study of hepatic pyruvate carboxylase activity in tumor rats. Biochem Biophys Res Commun 1991; 179:366-71; PMID:1883366; http://dx.doi.org/10.1016/0006-291X(91)91379-Q
68. Portais JC, Schuster R, Merle M, Canioni P. Metabolic flux determination in C6 glioma cells using carbon-13 distribution upon [1-13C]glucose incubation. Eur J Biochem 1993; 217:457-68; PMID:7901007; http://dx.doi.org/10.1111/j.1432- 1033.1993.tb18265.x
69. Wise DR, DeBerardinis RJ, Mancuso A, Sayed N, Zhang XY, Pfeiffer HK, et al. Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Proc Natl Acad Sci USA 2008; 105:18782-7; PMID:19033189; http://dx.doi.org/10.1073/pnas.0810199105
70. Albihn A, Johnsen JI, Henriksson MA. MYC in oncogenesis and as a target for cancer therapies. Adv Cancer Res 2010; 107:163-224; PMID:20399964; http://dx.doi.org/10.1016/S0065-230X(10)07006-5
71. Dang CV, Le A, Gao P. MYC-induced cancer cell energy metabolism and therapeutic opportunities. Clin Cancer Res 2009; 15:6479-83; PMID:19861459; http://dx.doi.org/10.1158/1078-0432.CCR-09-0889
72. 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; http:// dx.doi.org/10.1083/jcb. 200703099
73. Gao P, Tchernyshyov I, Chang TC, Lee YS, Kita K, Ochi T, et al. c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature 2009; 458:762-5; PMID: 19219026; http://dx.doi.org/10.1038/nature07823
74. Helmlinger G, Sckell A, Dellian M, Forbes NS, Jain RK. Acid production in glycolysis-impaired tumors provides new insights into tumor metabolism. Clin Cancer Res 2002; 8:1284-91; PMID:11948144
75. Deberardinis RJ, Sayed N, Ditsworth D, Thompson CB. Brick by brick: metabolism and tumor cell growth. Curr Opin Genet Dev 2008; 18:54-61; PMID: 18387799; http://dx.doi.org/10.1016/j.gde.2008.02.003
76. Mashima T, Seimiya H, Tsuruo T. De novo fatty-acid synthesis and related pathways as molecular targets for cancer therapy. Br J Cancer 2009; 100:1369-72; PMID:19352381; http://dx.doi.org/10.1038/sj.bjc.6605007
77. Liu M, Sjogren AK, Karlsson C, Ibrahim MX, Andersson KM, Olofsson FJ, et al. Targeting the protein prenyltransferases efficiently reduces tumor development in mice with K-RAS-induced lung cancer. Proc Natl Acad Sci USA 2010; 107:6471-6; PMID: 20308544; http://dx.doi.org/10.1073/pnas.0908396107
78. Kawamura T, Kanno R, Fujii H, Suzuki T. Expression of liver-type fatty-acid-binding protein, fatty acid synthase and vascular endothelial growth factor in human lung carcinoma. Pathobiology 2005; 72:233-40; PMID: 16374067; http://dx.doi.org/10.1159/000089417
79. Visca P, Sebastiani V, Botti C, Diodoro MG, Lasagni RP, Romagnoli F, et al. Fatty acid synthase (FAS) is a marker of increased risk of recurrence in lung carcinoma. Anticancer Res 2004; 24:4169-73; PMID: 15736468
80. Migita T, Ruiz S, Fornari A, Fiorentino M, Priolo C, Zadra G, et al. Fatty acid synthase: a metabolic enzyme and candidate oncogene in prostate cancer. J Natl Cancer Inst 2009; 101:519-32; PMID:19318631; http://dx.doi.org/ 10.1093/jnci/djp030
81. Grunt TW, Wagner R, Grusch M, Berger W, Singer CF, Marian B, et al. Interaction between fatty acid synthase- and ErbB-systems in ovarian cancer cells. Biochem Biophys Res Commun 2009; 385:454-9; PMID:19467222; http://dx.doi.org/10.1016/j.bbrc. 2009.05.085
82. Ueda SM, Yap KL, Davidson B, Tian Y, Murthy V, Wang TL, et al. Expression of fatty acid synthase depends on NAC1 and is associated with recurrent ovarian serous carcinomas. J Oncol 2010; 2010:285191; PMID:20508725
83. Knowles LM, Smith JW. Genome-wide changes accompanying knockdown of fatty acid synthase in breast cancer. BMC Genomics 2007; 8:168; PMID: 17565694; http://dx.doi.org/10.1186/1471-2164-8-168
84. Sebastiani V, Visca P, Botti C, Santeusanio G, Galati GM, Piccini V, et al. Fatty acid synthase is a marker of increased risk of recurrence in endometrial carcinoma. Gynecol Oncol 2004; 92:101-5; PMID:14751145; http://dx.doi.org/10.1016/j.ygyno.2003.10.027
85. Tsuji T, Yoshinaga M, Togami S, Douchi T, Nagata Y. Fatty acid synthase expression and clinicopathological findings in endometrial cancer. Acta Obstet Gynecol Scand 2004; 83:586-90; PMID:15144342
86. Kearney KE, Pretlow TG, Pretlow TP. Increased expression of fatty acid synthase in human aberrant crypt foci: possible target for colorectal cancer prevention. Int J Cancer 2009; 125:249-52; PMID: 19358283; http://dx.doi.org/10. 1002/ijc.24356
87. Zhao W, Kridel S, Thorburn A, Kooshki M, Little J, Hebbar S, et al. Fatty acid synthase: a novel target for antiglioma therapy. Br J Cancer 2006; 95:869-78; PMID:16969344; http://dx.doi.org/10.1038/sj.bjc.6603350
88. Uddin S, Hussain AR, Ahmed M, Abubaker J, Al-Sanea N, Abduljabbar A, et al. High prevalence of fatty acid synthase expression in colorectal cancers in Middle Eastern patients and its potential role as a therapeutic target. Am J Gastroenterol 2009; 104: 1790-801; PMID:19491830; http://dx.doi.org/10.1038/ajg. 2009.230
89. Orita H, Coulter J, Lemmon C, Tully E, Vadlamudi A, Medghalchi SM, et al. Selective inhibition of fatty acid synthase for lung cancer treatment. Clin Cancer Res 2007; 13:7139-45; PMID:18056164
90. Beckner ME, Fellows-Mayle W, Zhang Z, Agostino NR, Kant JA, Day BW, et al. Identification of ATP citrate lyase as a positive regulator of glycolytic function in glioblastomas. Int J Cancer 2010; 126:2282-95; PMID:19795461
91. Zhang X, Varin E, Allouche S, Lu Y, Poulain L, Icard P. Effect of citrate on malignant pleural mesothelioma cells: a synergistic effect with cisplatin. Anticancer Res 2009; 29:1249-54; PMID:19414371
92. Boros LG, Torday JS, Lim S, Bassilian S, Cascante M, Lee WN. Transforming growth factor beta2 promotes glucose carbon incorporation into nucleic acid ribose through the nonoxidative pentose cycle in lung epithelial carcinoma cells. Cancer Res 2000; 60:1183-5; PMID:10728670
93. Torres VE, Boletta A, Chapman A, Gattone V, Pei Y, Qian Q, et al. Prospects for mTOR inhibitor use in patients with polycystic kidney disease and hamartomatous diseases. Clin J Am Soc Nephrol 2010; 5:1312-29; PMID:20498248; http://dx.doi.org/10.2215/CJN. 01360210
94. Gibbons JJ, Abraham RT, Yu K. Mammalian target of rapamycin: discovery of rapamycin reveals a signaling pathway important for normal and cancer cell growth. Semin Oncol 2009; 36:S3-S17; PMID:19963098; http://dx.doi.org/10.1053/j. seminoncol.2009.10.011
95. Bensaad K, Cheung EC, Vousden KH. Modulation of intracellular ROS levels by TIGAR controls autophagy. EMBO J 2009; 28:3015-26; PMID:19713938; http://dx.doi.org/10.1038/emboj.2009.242
96. Langbein S, Frederiks WM, zur Hausen A, Popa J, Lehmann J, Weiss C, et al. Metastasis is promoted by a bioenergetic switch: new targets for progressive renal cell cancer. Int J Cancer 2008; 122:2422-8; PMID: 18302154; http://dx.doi.org/10.1002/ijc.23403
97. 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; 124:2789-96; PMID:19253370; http://dx.doi.org/10.1002/ijc.24262
98. Frederiks WM, Vizan P, Bosch KS, Vreeling-Sindelárová H, Boren J, Cascante M. Elevated activity of the oxidative and non-oxidative pentose phosphate pathway in (pre)neoplastic lesions in rat liver. Int J Exp Pathol 2008; 89:232-40; PMID:18422600; http://dx.doi.org/10.1111/j.1365-2613. 2008.00582.x
99. Tian WN, Braunstein LD, Pang J, Stuhlmeier KM, Xi QC, Tian X, et al. Importance of glucose-6-phosphate dehydrogenase activity for cell growth. J Biol Chem 1998; 273:10609-17; PMID:9553122; http://dx.doi.org/10.1074/jbc.273.17. 10609
100. Langbein S, Zerilli M, Zur Hausen A, Staiger W, Rensch-Boschert K, Lukan N, et al. Expression of transketolase TKTL1 predicts colon and urothelial cancer patient survival: Warburg effect reinterpreted. Br J Cancer 2006; 94:578-85; PMID:16465194; http://dx.doi.org/10.1038/sj.bjc.6602962
101. Sun W, Liu Y, Glazer CA, Shao C, Bhan S, Demokan S, et al. TKTL1 is activated by promoter hypomethylation and contributes to head and neck squamous cell carcinoma carcinogenesis through increased aerobic glycolysis and HIF1alpha stabilization. Clin Cancer Res 2010; 16:857-66; PMID:20103683; http://dx.doi.org/10.1158/1078-0432.CCR-09-2604
102. Schultz H, Kähler D, Branscheid D, Vollmer E, Zabel P, Goldmann T. TKTL1 is overexpressed in a large portion of non-small cell lung cancer specimens. Diagn Pathol 2008; 3:35; PMID:18700018; http://dx.doi. org/10.1186/1746-1596-3-35
103. Xu X, Zur Hausen A, Coy JF, Löchelt M. Transketolase-like protein 1 (TKTL1) is required for rapid cell growth and full viability of human tumor cells. Int J Cancer 2009; 124:1330-7; PMID: 19065656; http://dx.doi.org/10.1002/ ijc.24078
104. Landt S, Jeschke S, Koeninger A, Thomas A, Heusner T, Korlach S, et al. Tumor-specific correlation of tumor M2 pyruvate kinase in pre-invasive, invasive and recurrent cervical cancer. Anticancer Res 2010; 30:375-81; PMID:20332442
105. Benesch C, Schneider C, Voelker HU, Kapp M, Caffier H, Krockenberger M, et al. The clinicopathological and prognostic relevance of pyruvate kinase M2 and pAkt expression in breast cancer. Anticancer Res 2010; 30:1689-94; PMID:20592362