Dysregulated metabolism contributes to oncogenesis

Seminars in Cancer Biology

Volumn 35, Issue , 2015, Pages S129-S150

  Hirschey, Matthew D ^a,b   DeBerardinis, Ralph J ^c   Diehl, Anna Mae E ^a   Drew, Janice E ^d   Frezza, Christian ^e   Green, Michelle F ^b   Jones, Lee W ^f   Ko, Young H ^g   Le, Anne ^h   Lea, Michael A ⁱ   Locasale, Jason W ^a,j   Longo, Valter D ^k   Lyssiotis, Costas A ^l   McDonnell, Eoin ^b   Mehrmohamadi, Mahya ^j   Michelotti, Gregory ^a   Muralidhar, Vinayak ^m,n   Murphy, Michael P ^o   Pedersen, Peter L ^h   Poore, Brad ^h   Raffaghello, Lizzia ^p   Rathmell, Jeffrey C ^a,b   Sivanand, Sharanya ^q   Vander Heiden, Matthew G ^m,n,r   Wellen, Kathryn E ^q   Amedei, Amedeo ^s   Amin, Amr ^t   Salman Ashraf, S ^t   Azmi, Asfar S ^u   Bhakta, Dipita ^v   Bisland, Alan ^w   Boosani, Chandra S ^x   Chen, Sophie ^y   Fujii, Hiromasa ^z   Georgakilas, Alexandros ^aa   Guha, Gunjan ^ab   Halicka, Dorota ^ac   Helferich, Bill ^ad   Honoki, Kanya ^z   Keith, W N ^w   Mohammed, Sulma ^ae   Niccolai, Elena ^s   Nowsheen, Somaira ^af   Yang, Xujuan ^ad   more..

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

^b DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^d ROWETT RESEARCH INSTITUTE   (United Kingdom)

^e UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^f MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^g UNIVERSITY OF MARYLAND   (United States)

^h JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

ⁱ RUTGERS NEW JERSEY MEDICAL SCHOOL   (United States)

^j Department of Obstetrics Gynecology   (United States)

^k UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^l UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^m MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

ⁿ HARVARD MEDICAL SCHOOL   (United States)

^o UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^p G GASLINI INSTITUTE   (Italy)

^q UNIVERSITY OF PENNSYLVANIA   (United States)

^r DANA FARBER CANCER INSTITUTE   (United States)

^s UNIVERSITY OF FLORENCE   (Italy)

^t UNITED ARAB EMIRATES UNIVERSITY   (United Arab Emirates)

^u WAYNE STATE UNIVERSITY   (United States)

^v VIT UNIVERSITY   (India)

^w UNIVERSITY OF GLASGOW   (United Kingdom)

^x CREIGHTON UNIVERSITY   (United States)

^y Ovarian and Prostate Cancer Research Trust Laboratory   (United Kingdom)

^z NARA MEDICAL UNIVERSITY   (Japan)

^aa NATIONAL TECHNICAL UNIVERSITY OF ATHENS   (Greece)

^ab SASTRA UNIVERSITY   (India)

^ac NEW YORK MEDICAL COLLEGE   (United States)

^ad UNIVERSITY OF ILLINOIS AT URBANA CHAMPAIGN   (United States)

^ae PURDUE UNIVERSITY   (United States)

^af MAYO CLINIC   (United States)

more..

Author keywords

Cancer metabolism; Cancer therapy; Host metabolism; Mitochondria; Warburg

Indexed keywords

CARCINOGENESIS; CELL PROLIFERATION; CELL TRANSFORMATION; ENERGY METABOLISM; GENETIC EPIGENESIS; GENETICS; HUMAN; METABOLISM; MITOCHONDRION; NEOPLASM; PATHOLOGY;

CARCINOGENESIS; CELL PROLIFERATION; CELL TRANSFORMATION, NEOPLASTIC; ENERGY METABOLISM; EPIGENESIS, GENETIC; HUMANS; METABOLIC NETWORKS AND PATHWAYS; MITOCHONDRIA; NEOPLASMS;

EID: 84962028922     PISSN: 1044579X     EISSN: 10963650     Source Type: Journal    
DOI: 10.1016/j.semcancer.2015.10.002     Document Type: Review

References (329)

1. Hanahan D., Weinberg Robert A. Hallmarks of cancer: the next generation. Cell 2011, 144:646-674.
2. Vogelstein B., Papadopoulos N., Velculescu V.E., Zhou S., Diaz L.A., Kinzler K.W. Cancer genome landscapes. Science 2013, 339:1546-1558.
3. Ringash J., Au H.J., Siu L.L., Shapiro J.D., Jonker D.J., Zalcberg J.R., et al. Quality of life in patients with K-RAS wild-type colorectal cancer: the CO.20 phase 3 randomized trial. Cancer 2014, 120:181-189.
4. Warburg O., Wind F., Negelein E. The metabolism of tumors in the body. J. Gen. Physiol. 1927, 8:519-530.
5. Warburg O., Posener K., Negelein E. E Ueber den Stoffwechsel der Tumoren. Biochem. Z. 1924, 319-344.
6. Pasteur L. Expériences et vues nouvelles sur la nature des fermentations. C. R. Acad. Sci. 1861, 52:1260-1264.
7. Keilin D., Keilin J. The History of Cell Respiration and Cytochrome 1966, Cambridge University Press.
8. Warburg O. On the origin of cancer cells. Science 1956, 123:309-314.
9. Bensinger S.J., Christofk H.R. New aspects of the Warburg effect in cancer cell biology. Semin. Cell Dev. Biol. 2012, 23:352-361.
10. Weinhouse S. Oxidative metabolism of neoplastic tissues. Advances in Cancer Research 1955, 269-325. Academic Press. P.G. Jeese, H. Alexander (Eds.).
11. Weinhouse S. On respiratory impairment in cancer cells. Science 1956, 124:267-269.
12. Racker E. Bioenergetics and the problem of tumor growth. Am. Sci. 1972, 60:56-63.
13. Pedersen P.L. Tumor mitochondria and the bioenergetics of cancer cells. Prog. Exp. Tumor Res. 1978, 22:190-274.
14. Thompson C.B. Metabolic enzymes as oncogenes or tumor suppressors. N. Engl. J. Med. 2009, 360:813-815.
15. Seyfried T.N., Flores R.E., Poff A.M., D'Agostino D.P. Cancer as a metabolic disease: implications for novel therapeutics. Carcinogenesis 2014, 35:515-527.
16. Elstrom R.L., Bauer D.E., Buzzai M., Karnauskas R., Harris M.H., Plas D.R., et al. Akt stimulates aerobic glycolysis in cancer cells. Cancer Res. 2004, 64:3892-3899.
17. Wieman H.L., Wofford J.A., Rathmell J.C. Cytokine stimulation promotes glucose uptake via phosphatidylinositol-3 kinase/Akt regulation of Glut1 activity and trafficking. Mol. Biol. Cell 2007, 18:1437-1446.
18. Gottlieb E., Tomlinson I.P. Mitochondrial tumour suppressors: a genetic and biochemical update. Nat. Rev. Cancer 2005, 5:857-866.
19. Rathmell J.C., Fox C.J., Plas D.R., Hammerman P.S., Cinalli R.M., Thompson C.B. Akt-directed glucose metabolism can prevent Bax conformation change and promote growth factor-independent survival. Mol. Cell. Biol. 2003, 23:7315-7328.
20. Deprez J., Vertommen D., Alessi D.R., Hue L., Rider M.H. Phosphorylation and activation of heart 6-phosphofructo-2-kinase by protein kinase B and other protein kinases of the insulin signaling cascades. J. Biol. Chem. 1997, 272:17269-17275.
21. Efeyan A., Serrano M. p53: guardian of the genome and policeman of the oncogenes. Cell Cycle 2007, 6:1006-1010.
22. Matoba S., Kang J.G., Patino W.D., Wragg A., Boehm M., Gavrilova O., et al. p53 regulates mitochondrial respiration. Science 2006, 312:1650-1653.
23. Bensaad K., Tsuruta A., Selak M.A., Vidal M.N., Nakano K., Bartrons R., et al. TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell 2006, 126:107-120.
24. Vander Heiden M.G., Cantley L.C., Thompson C.B. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 2009, 324:1029-1033.
25. DeBerardinis R.J., Lum J.J., Hatzivassiliou G., Thompson C.B. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab. 2008, 7:11-20.
26. DeBerardinis R.J., 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. U. S. A. 2007, 104:19345-19350.
27. Portais J.C., Voisin P., Merle M., Canioni P. Glucose and glutamine metabolism in C6 glioma cells studied by carbon 13 NMR. Biochimie 1996, 78:155-164.
28. Wise D.R., DeBerardinis R.J., Mancuso A., Sayed N., Zhang X.Y., Pfeiffer H.K., et al. Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Proc. Natl. Acad. Sci. U. S. A. 2008, 105:18782-18787.
29. 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.
30. Commisso C., Davidson S.M., Soydaner-Azeloglu R.G., Parker S.J., Kamphorst J.J., Hackett S., et al. Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells. Nature 2013, 497:633-637.
31. Kamphorst J.J., Cross J.R., Fan J., de Stanchina E., Mathew R., White E.P., et al. Hypoxic and Ras-transformed cells support growth by scavenging unsaturated fatty acids from lysophospholipids. Proc. Natl. Acad. Sci. U. S. A. 2013, 110:8882-8887.
32. Bustamante E., Morris H.P., Pedersen P.L. Energy metabolism of tumor cells requirement for a form of hexokinase with a propensity for mitochondrial binding. J. Biol. Chem. 1981, 256:8699-8704.
33. Bustamante E., Pedersen P.L. High aerobic glycolysis of rat hepatoma cells in culture: role of mitochondrial hexokinase. Proc. Natl. Acad. Sci. U. S. A. 1977, 74:3735-3739.
34. Nakashima R.A., Paggi M.G., Scott L.J., Pedersen P.L. Purification and characterization of a bindable form of mitochondrial bound hexokinase from the highly glycolytic AS-30D rat hepatoma cell line. Cancer Res. 1988, 48:913-919.
35. Nakashima R.A., Mangan P.S., Colombini M., Pedersen P.L. Hexokinase receptor complex in hepatoma mitochondria: evidence from N,N'-dicyclohexylcarbodiimide-labeling studies for the involvement of the pore-forming protein VDAC. Biochemistry 1986, 25:1015-1021.
36. Robey R.B., Hay N. Mitochondrial hexokinases, novel mediators of the antiapoptotic effects of growth factors and Akt. Oncogene 2006, 25:4683-4696.
37. Pastorino J.G., Hoek J.B. Hexokinase II: the integration of energy metabolism and control of apoptosis. Curr. Med. Chem. 2003, 10:1535-1551.
38. Ko Y.H., Pedersen P.L., Geschwind J.F. Glucose catabolism in the rabbit VX2 tumor model for liver cancer: characterization and targeting hexokinase. Cancer Lett. 2001, 173:83-91.
39. Ko Y.H., Smith B.L., Wang Y., Pomper M.G., Rini D.A., Torbenson M.S., et al. Advanced cancers: eradication in all cases using 3-bromopyruvate therapy to deplete ATP. Biochem. Biophys. Res. Commun. 2004, 324:269-275.
40. Pedersen P.L. 3-Bromopyruvate (3BP) a fast acting, promising, powerful, specific, and effective "small molecule" anti-cancer agent taken from labside to bedside: introduction to a special issue. J. Bioenerg. Biomembr. 2012, 44:1-6.
41. Ko Y.H., Verhoeven H.A., Lee M.J., Corbin D.J., Vogl T.J., Pedersen P.L. A translational study "case report" on the small molecule "energy blocker" 3-bromopyruvate (3BP) as a potent anticancer agent: from bench side to bedside. J. Bioenerg. Biomembr. 2012, 44:163-170.
42. Weber G., Lea M.A. The molecular correlation concept of neoplasia. Adv. Enzyme Regul. 1966, 4:115-145.
43. Van Schaftingen E., Jett M.F., Hue L., Hers H.G. Control of liver 6-phosphofructokinase by fructose 2,6-bisphosphate and other effectors. Proc. Natl. Acad. Sci. U. S. A. 1981, 78:3483-3486.
44. Chesney J., Mitchell R., Benigni F., Bacher M., Spiegel L., Al-Abed Y., et al. An inducible gene product for 6-phosphofructo-2-kinase with an AU-rich instability element: role in tumor cell glycolysis and the Warburg effect. Proc. Natl. Acad. Sci. U. S. A. 1999, 96:3047-3052.
45. Atsumi T., Chesney J., Metz C., Leng L., Donnelly S., Makita Z., et al. High expression of inducible 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (iPFK-2; PFKFB3) in human cancers. Cancer Res. 2002, 62:5881-5887.
46. 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, 86:174-179.
47. Minchenko A., Leshchinsky I., Opentanova I., Sang N., Srinivas V., Armstead V., et al. Hypoxia-inducible factor-1-mediated expression of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3) gene. Its possible role in the Warburg effect. J. Biol. Chem. 2002, 277:6183-6187.
48. Mendoza E.E., Pocceschi M.G., Kong X., Leeper D.B., Caro J., Limesand K.H., et al. Control of glycolytic flux by AMP-activated protein kinase in tumor cells adapted to low pH. Transl. Oncol. 2012, 5:208-216.
49. Novellasdemunt L., Obach M., Millan-Arino L., Manzano A., Ventura F., Rosa J.L., et al. Progestins activate 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) in breast cancer cells. Biochem. J. 2012, 442:345-356.
50. Reddy M.M., Fernandes M.S., Deshpande A., Weisberg E., Inguilizian H.V., Abdel-Wahab O., et al. The JAK2V617F oncogene requires expression of inducible phosphofructokinase/fructose-bisphosphatase 3 for cell growth and increased metabolic activity. Leukemia 2012, 26:481-489.
51. Colombo S.L., Palacios-Callender M., Frakich N., Carcamo S., Kovacs I., Tudzarova S., et al. Molecular basis for the differential use of glucose and glutamine in cell proliferation as revealed by synchronized HeLa cells. Proc. Natl. Acad. Sci. U. S. A. 2011, 108:21069-21074.
52. Moncada S., Higgs E.A., Colombo S.L. Fulfilling the metabolic requirements for cell proliferation. Biochem. J. 2012, 446:1-7.
53. Yalcin A., Clem B.F., Simmons A., Lane A., Nelson K., Clem A.L., et al. Nuclear targeting of 6-phosphofructo-2-kinase (PFKFB3) increases proliferation via cyclin-dependent kinases. J. Biol. Chem. 2009, 284:24223-24232.
54. Yang W., Zheng Y., Xia Y., Ji H., Chen X., Guo F., et al. ERK1/2-dependent phosphorylation and nuclear translocation of PKM2 promotes the Warburg effect. Nat. Cell Biol. 2012, 14:1295-1304.
55. Clem B., Telang S., Clem A., Yalcin A., Meier J., Simmons A., et al. Small-molecule inhibition of 6-phosphofructo-2-kinase activity suppresses glycolytic flux and tumor growth. Mol. Cancer Ther. 2008, 7:110-120.
56. Telang S., Clem B.F., Klarer A.C., Clem A.L., Trent J.O., Bucala R., et al. Small molecule inhibition of 6-phosphofructo-2-kinase suppresses T cell activation. J. Transl. Med. 2012, 10:95.
57. Clem B.F., O'Neal J., Tapolsky G., Clem A.L., Imbert-Fernandez Y., Kerr D.A., et al. Targeting 6-phosphofructo-2-kinase (PFKFB3) as a therapeutic strategy against cancer. Mol. Cancer Ther. 2013, 12:1461-1470.
58. Mazurek S., Boschek C.B., Hugo F., Eigenbrodt E. Pyruvate kinase type M2 and its role in tumor growth and spreading. Semin. Cancer Biol. 2005, 15:300-308.
59. Bluemlein K., Gruning N.M., Feichtinger R.G., Lehrach H., Kofler B., Ralser M. No evidence for a shift in pyruvate kinase PKM1 to PKM2 expression during tumorigenesis. Oncotarget 2011, 2:393-400.
60. Mazurek S. Pyruvate kinase type M2: a key regulator of the metabolic budget system in tumor cells. Int. J. Biochem. Cell Biol. 2011, 43:969-980.
61. Chaneton B., Gottlieb E. Rocking cell metabolism: revised functions of the key glycolytic regulator PKM2 in cancer. Trends Biochem. Sci. 2012, 37:309-316.
62. Lyssiotis C.A., Anastasiou D.J.W.L., Vander Heiden M.G., Christofk H.R., Cantley L.C. Cellular control mechanisms that regulate pyruvate kinase M2 activity and promote cancer growth. Biomed. Res. 2012, 23:213-217.
63. Gao X., Wang H., Yang J.J., Liu X., Liu Z.R. Pyruvate kinase M2 regulates gene transcription by acting as a protein kinase. Mol. Cell 2012, 45:598-609.
64. Hoshino A., Hirst J.A., Fujii H. Regulation of cell proliferation by interleukin-3-induced nuclear translocation of pyruvate kinase. J. Biol. Chem. 2007, 282:17706-17711.
65. 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, 145:732-744.
66. Stetak A., Veress R., Ovadi J., Csermely P., Keri G., Ullrich A. Nuclear translocation of the tumor marker pyruvate kinase M2 induces programmed cell death. Cancer Res. 2007, 67:1602-1608.
67. Yang W., Xia Y., Hawke D., Li X., Liang J., Xing D., et al. PKM2 phosphorylates histone H3 and promotes gene transcription and tumorigenesis. Cell 2012, 150:685-696.
68. Yang W., Xia Y., Ji H., Zheng Y., Liang J., Huang W., et al. Nuclear PKM2 regulates beta-catenin transactivation upon EGFR activation. Nature 2011, 480:118-122.
69. Ignacak J., Stachurska M.B. The dual activity of pyruvate kinase type M2 from chromatin extracts of neoplastic cells. Comp. Biochem. Physiol. B: Biochem. Mol. Biol. 2003, 134:425-433.
70. Diaz-Jullien C., Moreira D., Sarandeses C.S., Covelo G., Barbeito P., Freire M. The M2-type isoenzyme of pyruvate kinase phosphorylates prothymosin alpha in proliferating lymphocytes. Biochim. Biophys. Acta 2011, 1814:355-365.
71. Cortes-Cros M., Hemmerlin C., Ferretti S., Zhang J., Gounarides J.S., Yin H., et al. M2 isoform of pyruvate kinase is dispensable for tumor maintenance and growth. Proc. Natl. Acad. Sci. U. S. A. 2013, 110:489-494.
72. Vander Heiden M.G. Targeting cell metabolism in cancer patients. Sci. Transl. Med. 2010, 2:31ed1.
73. Christofk H.R., Vander Heiden M.G., Harris M.H., Ramanathan A., Gerszten R.E., Wei R., et al. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature 2008, 452:230-233.
74. Anastasiou D., Yu Y., Israelsen W.J., Jiang J.K., Boxer M.B., Hong B.S., et al. Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis. Nat. Chem. Biol. 2012, 8:839-847.
75. Kung C., Hixon J., Choe S., Marks K., Gross S., Murphy E., et al. Small molecule activation of PKM2 in cancer cells induces serine auxotrophy. Chem. Biol. 2012, 19:1187-1198.
76. Yacovan A., Ozeri R., Kehat T., Mirilashvili S., Sherman D., Aizikovich A., et al. 1-(sulfonyl)-5-(arylsulfonyl)indoline as activators of the tumor cell specific M2 isoform of pyruvate kinase. Bioorg. Med. Chem. Lett. 2012, 22:6460-6468.
77. Jiang J.K., Boxer M.B., Vander Heiden M.G., Shen M., Skoumbourdis A.P., Southall N., et al. Evaluation of thieno[3,2-b]pyrrole[3,2-d]pyridazinones as activators of the tumor cell specific M2 isoform of pyruvate kinase. Bioorg. Med. Chem. Lett. 2010, 20:3387-3393.
78. Boxer M.B., Jiang J.K., Vander Heiden M.G., Shen M., Skoumbourdis A.P., Southall N., et al. Evaluation of substituted N,N'-diarylsulfonamides as activators of the tumor cell specific M2 isoform of pyruvate kinase. J. Med. Chem. 2010, 53:1048-1055.
79. Walsh M.J., Brimacombe K.R., Veith H., Bougie J.M., Daniel T., Leister W., et al. 2-Oxo-N-aryl-1,2,3,4-tetrahydroquinoline-6-sulfonamides as activators of the tumor cell specific M2 isoform of pyruvate kinase. Bioorg. Med. Chem. Lett. 2011, 21:6322-6327.
80. Anastasiou D., Poulogiannis G., Asara J.M., Boxer M.B., Jiang J.K., Shen M., et al. Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses. Science 2011, 334:1278-1283.
81. Owen O.E., Kalhan S.C., Hanson R.W. The key role of anaplerosis and cataplerosis for citric acid cycle function. J. Biol. Chem. 2002, 277:30409-30412.
82. DeBerardinis R.J., Cheng T. Q's next: the diverse functions of glutamine in metabolism, cell biology and cancer. Oncogene 2010, 29:313-324.
83. Scriver C.R., Rosenberg L. Amino Acid Metabolism and its Disorders 1973, WB Saunders, Philadelphia.
84. Fan T.W.M., Tan J.L., McKinney M.M., Lane A.N. Stable isotope resolved metabolomics analysis of ribonucleotide and RNA metabolism in human lung cancer cells. Metabolomics 2012, 8:517-527.
85. Frieden C., Glutamate dehydrogenase.5.Relation of enzyme structure to catalytic function J. Biol. Chem. 1963, 238:3286.
86. Reitzer L.J., Wice B.M., Kennell D. Evidence that glutamine, not sugar is the major energy-source for cultured hela-cells. J. Biol. Chem. 1979, 254:2669-2676.
87. Gao P., Tchernyshyov I., Chang T.C., Lee Y.S., Kita K., Ochi T., et al. c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature 2009, 458. 762-U100.
88. Nicklin P., Bergman P., Zhang B.L., Triantafellow E., Wang H., Nyfeler B., et al. Bidirectional transport of amino acids regulates mTOR and autophagy. Cell 2009, 136:521-534.
89. Morrish F., Neretti N., Sedivy J.M., Hockenbery D.M. The oncogene c-Myc coordinates regulation of metabolic networks to enable rapid cell cycle entry. Cell Cycle 2008, 7:1054-1066.
90. Son J., Lyssiotis C.A., Ying H., Wang X., Hua S., Ligorio M., et al. Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway. Nature 2013, 496:101-105.
91. Le A., Lane A.N., Hamaker M., Bose S., Gouw A., Barbi J., et al. Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B cells. Cell Metab. 2012, 15:110-121.
92. Moreadith R.W., Lehninger A.L. The pathways of glutamate and glutamine oxidation by tumor-cell mitochondria - role of mitochondrial Nad(P)+-dependent malic enzyme. J. Biol. Chem. 1984, 259:6215-6221.
93. Thornburg J.M., Nelson K.K., Clem B.F., Lane A.N., Arumugam S., Simmons A., et al. Targeting aspartate aminotransferase in breast cancer. Breast Cancer Res. 2008, 10:R84.
94. Gaglio D., Metallo C.M., Gameiro P.A., Hiller K., Danna L.S., Balestrieri C., et al. Oncogenic K-Ras decouples glucose and glutamine metabolism to support cancer cell growth. Mol. Syst. Biol. 2011, 7:523.
95. Ahluwalia G.S., Grem J.L., Hao Z., Cooney D.A., Metabolism Action of amino-acid analog anticancer agents. Pharmacol. Ther. 1990, 46:243-271.
96. Elgadi K.M., Meguid R.A., Qian M., Souba W.W., Abcouwer S.F. Cloning and analysis of unique human glutaminase isoforms generated by tissue-specific alternative splicing. Physiol. Genomics 1999, 1:51-62.
97. Robinson M.M., McBryant S.J., Tsukamoto T., Rojas C., Ferraris D.V., Hamilton S.K., et al. Novel mechanism of inhibition of rat kidney-type glutaminase by bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES). Biochem. J. 2007, 406:407-414.
98. Yang C.D., Sudderth J., Dang T.Y., Bachoo R.G., McDonald J.G., DeBerardinis R.J. Glioblastoma cells require glutamate dehydrogenase to survive impairments of glucose metabolism or Akt signaling. Cancer Res. 2009, 69:7986-7993.
99. Yang C.S., Wang X., Lu G., Picinich S.C. Cancer prevention by tea: animal studies, molecular mechanisms and human relevance. Nat. Rev. Cancer 2009, 9:429-439.
100. Li M., Smith C.J., Walker M.T., Smith T.J. Novel inhibitors complexed with glutamate dehydrogenase: allosteric regulation by control of protein dynamics. J. Biol. Chem. 2009, 284:22988-23000.
101. Beuster G., Zarse K., Kaleta C., Thierbach R., Kiehntopf M., Steinberg P., et al. Inhibition of alanine aminotransferase in silico and in vivo promotes mitochondrial metabolism to impair malignant growth. J. Biol. Chem. 2011, 286:22323-22330.
102. Lyssiotis C.A., Son J., Cantley L.C., Kimmelman A.C. Pancreatic cancers rely on a novel glutamine metabolism pathway to maintain redox balance. Cell Cycle 2013, 12:1987-1988.
103. Papandreou I., Cairns R.A., Fontana L., Lim A.L., Denko N.C. HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metab. 2006, 3:187-197.
104. Kim J.W., Tchernyshyov I., Semenza G.L., Dang C.V. HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab. 2006, 3:177-185.
105. Mullen A.R., DeBerardinis R.J. Genetically-defined metabolic reprogramming in cancer. Trends Endocrinol. Metab. 2012, 23:552-559.
106. Metallo C.M., Gameiro P.A., Bell E.L., Mattaini K.R., Yang J., Hiller K., et al. Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia. Nature 2012, 481:380-384.
107. Mullen A.R., Wheaton W.W., Jin E.S., Chen P.H., Sullivan L.B., Cheng T., et al. Reductive carboxylation supports growth in tumour cells with defective mitochondria. Nature 2012, 481:385-388.
108. Weinberg F., Hamanaka R., Wheaton W.W., Weinberg S., Joseph J., Lopez M., et al. Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity. Proc. Natl. Acad. Sci. U. S. A. 2010, 107:8788-8793.
109. Wise D.R., Ward P.S., Shay J.E., Cross J.R., Gruber J.J., Sachdeva U.M., et al. Hypoxia promotes isocitrate dehydrogenase-dependent carboxylation of alpha-ketoglutarate to citrate to support cell growth and viability. Proc. Natl. Acad. Sci. U. S. A. 2011, 108:19611-19616.
110. Scott D.A., Richardson A.D., Filipp F.V., Knutzen C.A., Chiang G.G., Ronai Z.A., et al. Comparative metabolic flux profiling of melanoma cell lines: beyond the Warburg effect. J. Biol. Chem. 2011, 286:42626-42634.
111. Des Rosiers C., Fernandez C.A., David F., Brunengraber H. Reversibility of the mitochondrial isocitrate dehydrogenase reaction in the perfused rat liver. Evidence from isotopomer analysis of citric acid cycle, intermediates. J. Biol. Chem. 1994, 269:27179-27182.
112. Yoo H., Antoniewicz M.R., Stephanopoulos G., Kelleher J.K. Quantifying reductive carboxylation flux of glutamine to lipid in a brown adipocyte cell line. J. Biol. Chem. 2008, 283:20621-20627.
113. Comte B., Vincent G., Bouchard B., Benderdour M., Des Rosiers C. Reverse flux through cardiac NADP(+)-isocitrate dehydrogenase under normoxia and ischemia. Am. J. Physiol. Heart Circ. Physiol. 2002, 283:H1505-H1514.
114. Lemons J.M., Feng X.J., Bennett B.D., Legesse-Miller A., Johnson E.L., Raitman I., et al. Quiescent fibroblasts exhibit high metabolic activity. PLoS Biol. 2010, 8:e1000514.
115. Gameiro P.A., Yang J., Metelo A.M., Perez-Carro R., Baker R., Wang Z., et al. In vivo HIF-mediated reductive carboxylation is regulated by citrate levels and sensitizes VHL-deficient cells to glutamine deprivation. Cell Metab. 2013, 17:372-385.
116. Pedersen A., Karlsson G.B., Rydstrom J. Proton-translocating transhydrogenase: an update of unsolved and controversial issues. J. Bioenerg. Biomembr. 2008, 40:463-473.
117. Gameiro P.A., Laviolette L.A., Kelleher J.K., Iliopoulos O., Stephanopoulos G. Cofactor balance by nicotinamide nucleotide transhydrogenase (NNT) coordinates reductive carboxylation and glucose catabolism in the TCA cycle. J. Biol. Chem. 2013.
118. Rajagopalan K.N., Egnatchik R.A., Calvaruso M.A., Wasti A.T., Padanad M.S., Boroughs L.K., et al. Metabolic plasticity maintains proliferation in pyruvate dehydrogenase deficient cells. Cancer Metab. 2015, 3:7.
119. Currie E., Schulze A., Zechner R., Walther T.C., Farese R.V. Cellular fatty acid metabolism and cancer. Cell Metab. 2013, 18:153-161.
120. Lu C., Thompson C.B. Metabolic regulation of epigenetics. Cell Metab. 2012, 16:9-17.
121. Katada S., Imhof A., Sassone-Corsi P. Connecting threads: epigenetics and metabolism. Cell 2012, 148:24-28.
122. Wellen K.E., Thompson C.B. A two-way street: reciprocal regulation of metabolism and signalling. Nat. Rev. Mol. Cell Biol. 2012, 13:270-276.
123. Yun J., Johnson J.L., Hanigan C.L., Locasale J.W. Interactions between epigenetics and metabolism in cancers. Front. Oncol. 2012, 2:163.
124. Kaelin W.G., McKnight S.L. Influence of metabolism on epigenetics and disease. Cell 2013, 153:56-69.
125. Dawson M.A., Kouzarides T. Cancer epigenetics: from mechanism to therapy. Cell 2012, 150:12-27.
126. Vander Heiden M.G. Targeting cancer metabolism: a therapeutic window opens. Nat. Rev. Drug Discov. 2011, 10:671-684.
127. Love D.C., Hanover J.A. The hexosamine signaling pathway: deciphering the "O-GlcNAc code". Sci. STKE 2005, 2005:re13.
128. Hart G.W., Slawson C., Ramirez-Correa G., Lagerlof O. Cross talk between O-GlcNAcylation and phosphorylation: roles in signaling, transcription, and chronic disease. Annu. Rev. Biochem. 2011, 80:825-858.
129. Lynch T.P., Ferrer C.M., Jackson S.R., Shahriari K.S., Vosseller K., Reginato M.J. Critical role of O-linked beta-N-acetylglucosamine transferase in prostate cancer invasion, angiogenesis, and metastasis. J. Biol. Chem. 2012, 287:11070-11081.
130. Caldwell S.A., Jackson S.R., Shahriari K.S., Lynch T.P., Sethi G., Walker S., et al. Nutrient sensor O-GlcNAc transferase regulates breast cancer tumorigenesis through targeting of the oncogenic transcription factor FoxM1. Oncogene 2010, 29:2831-2842.
131. Yi W., Clark P.M., Mason D.E., Keenan M.C., Hill C., Goddard W.A., et al. Phosphofructokinase 1 glycosylation regulates cell growth and metabolism. Science 2012, 337:975-980.
132. Zhang S., Roche K., Nasheuer H.P., Lowndes N.F. Modification of histones by sugar beta-N-acetylglucosamine (GlcNAc) occurs on multiple residues, including histone H3 serine 10, and is cell cycle-regulated. J. Biol. Chem. 2011, 286:37483-37495.
133. Sakabe K., Wang Z., Hart G.W. Beta-N-acetylglucosamine (O-GlcNAc) is part of the histone code. Proc. Natl. Acad. Sci. U. S. A. 2010, 107:19915-19920.
134. Fujiki R., Hashiba W., Sekine H., Yokoyama A., Chikanishi T., Ito S., et al. GlcNAcylation of histone H2B facilitates its monoubiquitination. Nature 2011, 480:557-560.
135. Fong J.J., Nguyen B.L., Bridger R., Medrano E.E., Wells L., Pan S., et al. Beta-N-Acetylglucosamine (O-GlcNAc) is a novel regulator of mitosis-specific phosphorylations on histone H3. J. Biol. Chem. 2012, 287:12195-12203.
136. Chen Q., Chen Y., Bian C., Fujiki R., Yu X. TET2 promotes histone O-GlcNAcylation during gene transcription. Nature 2012.
137. Vella P., Scelfo A., Jammula S., Chiacchiera F., Williams K., Cuomo A., et al. Tet proteins connect the O-linked N-acetylglucosamine transferase Ogt to chromatin in embryonic stem cells. Mol. Cell 2013, 49:645-656.
138. Deplus R., Delatte B., Schwinn M.K., Defrance M., Mendez J., Murphy N., et al. TET2 and TET3 regulate GlcNAcylation and H3K4 methylation through OGT and SET1/COMPASS. EMBO J. 2013, 32:645-655.
139. Zhang Q., Liu X., Gao W., Li P., Hou J., Li J., et al. Differential regulation of the ten-eleven translocation (TET) family of dioxygenases by O-linked beta-N-acetylglucosamine transferase (OGT). J. Biol. Chem. 2014, 289:5986-5996.
140. Quivoron C., Couronne L., Della Valle V., Lopez C.K., Plo I., Wagner-Ballon O., et al. TET2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis. Cancer Cell 2011, 20:25-38.
141. Figueroa M.E., Abdel-Wahab O., Lu C., Ward P.S., Patel J., Shih A., et al. Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell 2010, 18:553-567.
142. Figueroa M.E., Lugthart S., Li Y., Erpelinck-Verschueren C., Deng X., Christos P.J., et al. DNA methylation signatures identify biologically distinct subtypes in acute myeloid leukemia. Cancer Cell 2010, 17:13-27.
143. You J.S., Jones P.A. Cancer genetics and epigenetics: two sides of the same coin?. Cancer Cell 2012, 22:9-20.
144. Sutter B.M., Wu X., Laxman S., Tu B.P. Methionine inhibits autophagy and promotes growth by inducing the SAM-responsive methylation of PP2A. Cell 2013, 154:403-415.
145. Cavuoto P., Fenech M.F. A review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension. Cancer Treat. Rev. 2012, 38:726-736.
146. Ulanovskaya O.A., Zuhl A.M., Cravatt B.F. NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink. Nat. Chem. Biol. 2013, 9:300-306.
147. Shyh-Chang N., Locasale J.W., Lyssiotis C.A., Zheng Y., Teo R.Y., Ratanasirintrawoot S., et al. Influence of threonine metabolism on S-adenosylmethionine and histone methylation. Science 2013, 339:222-226.
148. Katoh Y., Ikura T., Hoshikawa Y., Tashiro S., Ito T., Ohta M., et al. Methionine adenosyltransferase II serves as a transcriptional corepressor of Maf oncoprotein. Mol. Cell 2011, 41:554-566.
149. Wellen K.E., Hatzivassiliou G., Sachdeva U.M., Bui T.V., Cross J.R., Thompson C.B. ATP-citrate lyase links cellular metabolism to histone acetylation. Science 2009, 324:1076-1080.
150. Friis R.M., Wu B.P., Reinke S.N., Hockman D.J., Sykes B.D., Schultz M.C. A glycolytic burst drives glucose induction of global histone acetylation by picNuA4 and SAGA. Nucleic Acids Res. 2009, 37:3969-3980.
151. Cai L., Sutter B.M., Li B., Tu B.P. Acetyl-CoA induces cell growth and proliferation by promoting the acetylation of histones at growth genes. Mol. Cell 2011, 42:426-437.
152. Takahashi H., McCaffery J.M., Irizarry R.A., Boeke J.D. Nucleocytosolic acetyl-coenzyme a synthetase is required for histone acetylation and global transcription. Mol. Cell 2006, 23:207-217.
153. Sassone-Corsi P. When metabolism and epigenetics converge. Science 2013, 339:148-150.
154. Houtkooper R.H., Pirinen E., Auwerx J. Sirtuins as regulators of metabolism and healthspan. Nat. Rev. Mol. Cell Biol. 2012, 13:225-238.
155. Fulco M., Cen Y., Zhao P., Hoffman E.P., McBurney M.W., Sauve A.A., et al. Glucose restriction inhibits skeletal myoblast differentiation by activating SIRT1 through AMPK-mediated regulation of Nampt. Dev. Cell 2008, 14:661-673.
156. Canto C., Gerhart-Hines Z., Feige J.N., Lagouge M., Noriega L., Milne J.C., et al. AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature 2009, 458:1056-1060.
157. Shimazu T., Hirschey M.D., Newman J., He W., Shirakawa K., Le Moan N., et al. Suppression of oxidative stress by beta-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science 2013, 339:211-214.
158. Chypre M., Zaidi N., Smans K. ATP-citrate lyase: a mini-review. Biochem. Biophys. Res. Commun. 2012, 422:1-4.
159. Seligson D.B., Horvath S., McBrian M.A., Mah V., Yu H., Tze S., et al. Global levels of histone modifications predict prognosis in different cancers. Am. J. Pathol. 2009, 174:1619-1628.
160. Barlesi F., Giaccone G., Gallegos-Ruiz M.I., Loundou A., Span S.W., Lefesvre P., et al. Global histone modifications predict prognosis of resected non small-cell lung cancer. J. Clin. Oncol. 2007, 25:4358-4364.
161. Elsheikh S.E., Green A.R., Rakha E.A., Powe D.G., Ahmed R.A., Collins H.M., et al. Global histone modifications in breast cancer correlate with tumor phenotypes, prognostic factors, and patient outcome. Cancer Res. 2009, 69:3802-3809.
162. Seligson D.B., Horvath S., Shi T., Yu H., Tze S., Grunstein M., et al. Global histone modification patterns predict risk of prostate cancer recurrence. Nature 2005, 435:1262-1266.
163. Bianco-Miotto T., Chiam K., Buchanan G., Jindal S., Day T.K., Thomas M., et al. Global levels of specific histone modifications and an epigenetic gene signature predict prostate cancer progression and development. Cancer Epidemiol. Biomark. Prev. 2010, 19:2611-2622.
164. Carafa V., Nebbioso A., Altucci L. Sirtuins and disease: the road ahead. Front. Pharmacol. 2012, 3:4.
165. Anderson K.A., Green M.F., Huynh F.K., Wagner G.R., Hirschey M.D. SnapShot: mammalian sirtuins. Cell 2014, 159:956-961.
166. Lombard D.B., Alt F.W., Cheng H.L., Bunkenborg J., Streeper R.S., Mostoslavsky R., et al. Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Mol. Cell. Biol. 2007, 27:8807-8814.
167. Nemoto S., Fergusson M.M., Finkel T. Nutrient availability regulates SIRT1 through a forkhead-dependent pathway. Science 2004, 306:2105-2108.
168. Stunkel W., Campbell R.M. Sirtuin 1 (SIRT1): the misunderstood HDAC. J. Biomol. Screen. 2011, 16:1153-1169.
169. Deng C.X. SIRT1, is it a tumor promoter or tumor suppressor?. Int. J. Biol. Sci. 2009, 5:147-152.
170. Banks A.S., Kon N., Knight C., Matsumoto M., Gutierrez-Juarez R., Rossetti L., et al. SirT1 gain of function increases energy efficiency and prevents diabetes in mice. Cell Metab. 2008, 8:333-341.
171. Wang R.H., Sengupta K., Li C., Kim H.S., Cao L., Xiao C., et al. Impaired DNA damage response, genome instability, and tumorigenesis in SIRT1 mutant mice. Cancer Cell 2008, 14:312-323.
172. Wang R.H., Zheng Y., Kim H.S., Xu X., Cao L., Luhasen T., et al. Interplay among BRCA1 SIRT1, and survivin during BRCA1-associated tumorigenesis. Mol. Cell 2008, 32:11-20.
173. Hirschey M.D., Shimazu T., Goetzman E., Jing E., Schwer B., Lombard D.B., et al. SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation. Nature 2010, 464:121-125.
174. Kim H.S., Patel K., Muldoon-Jacobs K., Bisht K.S., Aykin-Burns N., Pennington J.D., et al. SIRT3 is a mitochondria-localized tumor suppressor required for maintenance of mitochondrial integrity and metabolism during stress. Cancer Cell 2010, 17:41-52.
175. Finley L.W., Carracedo A., Lee J., Souza A., Egia A., Zhang J., et al. SIRT3 opposes reprogramming of cancer cell metabolism through HIF1alpha destabilization. Cancer Cell 2011, 19:416-428.
176. Jeong S.M., Xiao C., Finley L.W., Lahusen T., Souza A.L., Pierce K., et al. SIRT4 has tumor-suppressive activity and regulates the cellular metabolic response to DNA damage by inhibiting mitochondrial glutamine metabolism. Cancer Cell 2013, 23:450-463.
177. Sebastian C., Zwaans B.M., Silberman D.M., Gymrek M., Goren A., Zhong L., et al. The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism. Cell 2012, 151:1185-1199.
178. Marquardt J.U., Fischer K., Baus K., Kashyap A., Ma S., Krupp M., et al. SIRT6 dependent genetic and epigenetic alterations are associated with poor clinical outcome in HCC patients. Hepatology 2013.
179. Cohen H.Y., Miller C., Bitterman K.J., Wall N.R., Hekking B., Kessler B., et al. Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science 2004, 305:390-392.
180. Hirschey M.D., Shimazu T., Jing E., Grueter C.A., Collins A.M., Aouizerat B., et al. SIRT3 deficiency and mitochondrial protein hyperacetylation accelerate the development of the metabolic syndrome. Mol. Cell 2011, 44:177-190.
181. Tong X., Zhao F., Thompson C.B. The molecular determinants of de novo nucleotide biosynthesis in cancer cells. Curr. Opin. Genet. Dev. 2009, 19:32-37.
182. Finkelstein J.D. Methionine metabolism in mammals. J. Nutr. Biochem. 1990, 1:228-237.
183. Zatz M., Dudley P.A., Kloog Y., Markey S.P. Nonpolar lipid methylation. Biosynthesis of fatty acid methyl esters by rat lung membranes using S-adenosylmethionine. J. Biol. Chem. 1981, 256:10028-10032.
184. Anderson O.S., Sant K.E., Dolinoy D.C. Nutrition and epigenetics: an interplay of dietary methyl donors, one-carbon metabolism and DNA methylation. J. Nutr. Biochem. 2012, 23:853-859.
185. Teperino R., Schoonjans K., Auwerx J. Histone methyl transferases and demethylases; can they link metabolism and transcription?. Cell Metab. 2010, 12:321-327.
186. Yang Y., Bedford M.T. Protein arginine methyltransferases and cancer. Nat. Rev. Cancer 2013, 13:37-50.
187. Snell K. Enzymes of serine metabolism in normal, developing and neoplastic rat tissues. Adv. Enzyme Regul. 1984, 22:325-400.
188. Snell K., Natsumeda Y., Weber G. The modulation of serine metabolism in hepatoma 3924A during different phases of cellular proliferation in culture. Biochem. J. 1987, 245:609-612.
189. Locasale J.W., Grassian A.R., Melman T., Lyssiotis C.A., Mattaini K.R., Bass A.J., et al. Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis. Nat. Genet. 2011, 43:869-874.
190. Possemato R., Marks K.M., Shaul Y.D., Pacold M.E., Kim D., Birsoy K., et al. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature 2011, 476:346-350.
191. Pollari S., Kakonen S.M., Edgren H., Wolf M., Kohonen P., Sara H., et al. Enhanced serine production by bone metastatic breast cancer cells stimulates osteoclastogenesis. Breast Cancer Res. Treat. 2011, 125:421-430.
192. Jain M., Nilsson R., Sharma S., Madhusudhan N., Kitami T., Souza A.L., et al. Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation. Science 2012, 336:1040-1044.
193. Zhang W.C., Shyh-Chang N., Yang H., Rai A., Umashankar S., Ma S., et al. Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis. Cell 2012, 148:259-272.
194. Hu C.M., Yeh M.T., Tsao N., Chen C.W., Gao Q.Z., Chang C.Y., et al. Tumor cells require thymidylate kinase to prevent dUTP incorporation during DNA repair. Cancer Cell 2012, 22:36-50.
195. Chabner B.A., Roberts T.G. Timeline: chemotherapy and the war on cancer. Nat. Rev. Cancer 2005, 5:65-72.
196. Diasio R.B., Harris B.E. Clinical pharmacology of 5-fluorouracil. Clin. Pharmacokinet. 1989, 16:215-237.
197. Casero R.A., Marton L.J. Targeting polyamine metabolism and function in cancer and other hyperproliferative diseases. Nat. Rev. Drug Discov. 2007, 6:373-390.
198. Cheong H., Lu C., Lindsten T., Thompson C.B. Therapeutic targets in cancer cell metabolism and autophagy. Nat. Biotechnol. 2012, 30:671-678.
199. Maddocks O.D., Berkers C.R., Mason S.M., Zheng L., Blyth K., Gottlieb E., et al. Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. Nature 2013, 493:542-546.
200. Sreekumar A., Poisson L.M., Rajendiran T.M., Khan A.P., Cao Q., Yu J., et al. Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature 2009, 457:910-914.
201. Vazquez A., Tedeschi P.M., Bertino J.R. Overexpression of the mitochondrial folate and glycine-serine pathway: a new determinant of methotrexate selectivity in tumors. Cancer Res. 2013, 73:478-482.
202. Pansuriya T.C., van Eijk R., d'Adamo P., van Ruler M.A., Kuijjer M.L., Oosting J., et al. Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome. Nat. Genet. 2011, 43:1256-1261.
203. Parsons D.W., Jones SN, Zhang X., Lin J.C.-H., Leary R.J., Angenendt P., et al. An integrated genomic analysis of human glioblastoma multiforme. Science 2008, 321:1807-1812.
204. Gross S., Cairns R.A., Minden M.D., Driggers E.M., Bittinger M.A., Jang H.G., et al. Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations. J. Exp. Med. 2010, 207:339-344.
205. Turcan S., Rohle D., Goenka A., Walsh L.A., Fang F., Yilmaz E., et al. IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype. Nature 2012, 483:479-483.
206. Losman J.A., Kaelin W.G. What a difference a hydroxyl makes: mutant IDH (R)-2-hydroxyglutarate and cancer. Genes Dev. 2013, 27:836-852.
207. Dang L., White D.W., Gross S., Bennett B.D., Bittinger M.A., Driggers E.M., et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 2009, 462:739-744.
208. Ward P.S., Patel J., Wise D.R., Abdel-Wahab O., Bennett B.D., Coller H.A., et al. The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. Cancer Cell 2010, 17:225-234.
209. Kats L.M., Reschke M., Taulli R., Pozdnyakova O., Burgess K., Bhargava P., et al. Proto-oncogenic role of mutant IDH2 in leukemia initiation and maintenance. Cell Stem Cell 2014.
210. Lu C., Venneti S., Akalin A., Fang F., Ward P.S., Dematteo R.G., et al. Induction of sarcomas by mutant IDH2. Genes Dev. 2013, 27:1986-1998.
211. Xu W., Yang H., Liu Y., Yang Y., Wang P., Kim S.H., et al. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases. Cancer Cell 2011, 19:17-30.
212. Chowdhury R., Yeoh K.K., Tian Y.M., Hillringhaus L., Bagg E.A., Rose N.R., et al. The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases. EMBO Rep. 2011, 12:463-469.
213. Losman J.A., Looper R.E., Koivunen P., Lee S., Schneider R.K., McMahon C., et al. (R)-2-hydroxyglutarate is sufficient to promote leukemogenesis and its effects are reversible. Science 2013, 339:1621-1625.
214. Koivunen P., Lee S., Duncan C.G., Lopez G., Lu G., Ramkissoon S., et al. Transformation by the (R)-enantiomer of 2-hydroxyglutarate linked to EGLN activation. Nature 2012, 483:484-488.
215. DiNardo C.D., Propert K.J., Loren A.W., Paietta E., Sun Z., Levine R.L., et al. Serum 2-hydroxyglutarate levels predict isocitrate dehydrogenase mutations and clinical outcome in acute myeloid leukemia. Blood 2013, 121:4917-4924.
216. Choi C., Ganji S.K., DeBerardinis R.J., Hatanpaa K.J., Rakheja D., Kovacs Z., et al. 2-hydroxyglutarate detection by magnetic resonance spectroscopy in IDH-mutated patients with gliomas. Nat. Med. 2012, 18:624-629.
217. Wang F., Travins J., Delabarre B., Penard-Lacronique V., Schalm S., Hansen E., et al. Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiation. Science (New York, NY) 2013, 340:622-626.
218. Rohle D., Popovici-Muller J., Palaskas N., Turcan S., Grommes C., Campos C., et al. An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells. Science (New York, NY) 2013.
219. Selak M.A., Armour S.M., MacKenzie E.D., Boulahbel H., Watson D.G., Mansfield K.D., et al. Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase. Cancer Cell 2005, 7:77-85.
220. Xiao M., Yang H., Xu W., Ma S., Lin H., Zhu H., et al. Inhibition of alpha-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors. Genes Dev. 2012, 26:1326-1338.
221. Killian J.K., Kim S.Y., Miettinen M., Smith C., Merino M., Tsokos M., et al. Succinate dehydrogenase mutation underlies global epigenomic divergence in gastrointestinal stromal tumor. Cancer Discov. 2013, 3:648-657.
222. Letouze E., Martinelli C., Loriot C., Burnichon N., Abermil N., Ottolenghi C., et al. SDH mutations establish a hypermethylator phenotype in paraganglioma. Cancer Cell 2013, 23:739-752.
223. Colegio O.R., Chu N.Q., Szabo A.L., Chu T., Rhebergen A.M., Jairam V., et al. Functional polarization of tumour-associated macrophages by tumour-derived lactic acid. Nature 2014, 513:559-563.
224. Pavlides S., Whitaker-Menezes D., Castello-Cros R., Flomenberg N., Witkiewicz A.K., Frank P.G., et al. The reverse Warburg effect: aerobic glycolysis in cancer associated fibroblasts and the tumor stroma. Cell Cycle 2009, 8:3984-4001.
225. Kroemer G., Pouyssegur J. Tumor cell metabolism: cancer's Achilles' heel. Cancer Cell 2008, 13:472-482.
226. Granchi C., Bertini S., Macchia M., Minutolo F. Inhibitors of lactate dehydrogenase isoforms and their therapeutic potentials. Curr. Med. Chem. 2010, 17:672-697.
227. Fantin V.R., St-Pierre J., Leder P. Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer Cell 2006, 9:425-434.
228. Le A., Cooper C.R., Gouw A.M., Dinavahi R., Maitra A., Deck L.M., et al. Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression. Proc. Natl. Acad. Sci. U. S. A. 2010, 107:2037-2042.
229. Seth P., Grant A., Tang J., Vinogradov E., Wang X., Lenkinski R., et al. On-target inhibition of tumor fermentative glycolysis as visualized by hyperpolarized pyruvate. Neoplasia 2011, 13:60-71.
230. Shim H., Dolde C., Lewis B.C., Wu C.S., Dang G., Jungmann R.A., et al. c-Myc transactivation of LDH-A: implications for tumor metabolism and growth. Proc. Natl. Acad. Sci. U. S. A. 1997, 94:6658-6663.
231. Zhao Y., Liu H., Riker A.I., Fodstad O., Ledoux S.P., Wilson G.L., et al. Emerging metabolic targets in cancer therapy. Front. Biosci. 2011, 16:1844-1860.
232. Zhou M., Zhao Y., Ding Y., Liu H., Liu Z., Fodstad O., et al. Warburg effect in chemosensitivity: targeting lactate dehydrogenase-A re-sensitizes taxol-resistant cancer cells to taxol. Mol. Cancer 2010, 9:33.
233. Bonen A. Lactate transporters (MCT proteins) in heart and skeletal muscles. Med. Sci. Sports Exerc. 2000, 32:778-789.
234. Hussien R., Brooks G.A. Mitochondrial and plasma membrane lactate transporter and lactate dehydrogenase isoform expression in breast cancer cell lines. Physiol. Genomics 2011, 43:255-264.
235. Sonveaux P., Vegran F., Schroeder T., Wergin M.C., Verrax J., Rabbani Z.N., et al. Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice. J. Clin. Invest. 2008, 118:3930-3942.
236. Miranda-Goncalves V., Honavar M., Pinheiro C., Martinho O., Pires M.M., Pinheiro C., et al. Monocarboxylate transporters (MCTs) in gliomas: expression and exploitation as therapeutic targets. Neuro-Oncology 2013, 15:172-188.
237. Smith R.A., Hartley R.C., Cocheme H.M., Murphy M.P. Mitochondrial pharmacology. Trends Pharmacol. Sci. 2012, 33:341-352.
238. Smith R.A., Hartley R.C., Murphy M.P. Mitochondria-targeted small molecule therapeutics and probes. Antioxid. Redox Signal. 2011, 15:3021-3038.
239. Wallace D.C., Fan W., Procaccio V. Mitochondrial energetics and therapeutics. Annu. Rev. Pathol. 2010, 5:297-348.
240. Calvo S.E., Mootha V.K. The mitochondrial proteome and human disease. Annu. Rev. Genomics Hum. Genet. 2010, 11:25-44.
241. Green D.R., Galluzzi L., Kroemer G. Mitochondria the autophagy-inflammation-cell death axis in organismal aging. Science 2011, 333:1109-1112.
242. Viscomi C., Bottani E., Civiletto G., Cerutti R., Moggio M., Fagiolari G., et al. In vivo correction of COX deficiency by activation of the AMPK/PGC-1alpha axis. Cell Metab. 2011, 14:80-90.
243. Ventura-Clapier R., Garnier A., Veksler V. Transcriptional control of mitochondrial biogenesis: the central role of PGC-1alpha. Cardiovasc. Res. 2008, 79:208-217.
244. Michelakis E.D., Webster L., Mackey J.R. Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer. Br. J. Cancer 2008, 99:989-994.
245. Lopez-Armada M.J., Riveiro-Naveira R.R., Vaamonde-Garcia C., Valcarcel-Ares M.N. Mitochondrial dysfunction and the inflammatory response. Mitochondrion 2013, 13:106-118.
246. Wallace D.C. Mitochondria and cancer. Nat. Rev. Cancer 2012, 12:685-698.
247. Fulda S., Galluzzi L., Kroemer G. Targeting mitochondria for cancer therapy. Nat. Rev. Drug Discov. 2010, 9:447-464.
248. Longo V.D., Fontana L. Calorie restriction and cancer prevention: metabolic and molecular mechanisms. Trends Pharmacol. Sci. 2010, 31:89-98.
249. Lee C., Safdie F.M., Raffaghello L., Wei M., Madia F., Parrella E., et al. Reduced levels of IGF-I mediate differential protection of normal and cancer cells in response to fasting and improve chemotherapeutic index. Cancer Res. 2010, 70:1564-1572.
250. Pallavi R., Giorgio M., Pelicci P.G. Insights into the beneficial effect of caloric/dietary restriction for a healthy and prolonged life. Front. Physiol. 2012, 3:318.
251. Tannenbaum A., Silverstone H. The influence of the degree of caloric restriction on the formation of skin tumors and hepatomas in mice. Cancer Res. 1949, 9:724-727.
252. Silverstone H., Tannenbaum A. Proportion of dietary protein and the formation of spontaneous hepatomas in the mouse. Cancer Res. 1951, 11:442-446.
253. Tannenbaum A., Silverstone H. Effect of limited food intake on survival of mice bearing spontaneous mammary carcinoma and on the incidence of lung metastases. Cancer Res. 1953, 13:532-536.
254. Ruggeri B.A., Klurfeld D.M., Kritchevsky D., Furlanetto R.W. Caloric restriction and 7,12-dimethylbenz(a)anthracene-induced mammary tumor growth in rats: alterations in circulating insulin, insulin-like growth factors I and II, and epidermal growth factor. Cancer Res. 1989, 49:4130-4134.
255. Colman R.J., Anderson R.M., Johnson S.C., Kastman E.K., Kosmatka K.J., Beasley T.M., et al. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science 2009, 325:201-204.
256. Mattison J.A., Roth G.S., Beasley T.M., Tilmont E.M., Handy A.M., Herbert R.L., et al. Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature 2012, 489:318-321.
257. Kalaany N.Y., Sabatini D.M. Tumours with PI3K activation are resistant to dietary restriction. Nature 2009, 458:725-731.
258. Laviano A., Seelaender M., Sanchez-Lara K., Gioulbasanis I., Molfino A., Rossi Fanelli F. Beyond anorexia-cachexia. Nutrition and modulation of cancer patients' metabolism: supplementary, complementary or alternative anti-neoplastic therapy?. Eur. J. Pharmacol. 2011, 668(Suppl. 1):S87-S90.
259. Kubo C., Day N.K., Good R.A. Influence of early or late dietary restriction on life span and immunological parameters in MRL/Mp-lpr/lpr mice. Proc. Natl. Acad. Sci. U. S. A. 1984, 81:5831-5835.
260. Hunt N.D., Li G.D., Zhu M., Miller M., Levette A., Chachich M.E., et al. Effect of calorie restriction and refeeding on skin wound healing in the rat. Age (Dordr) 2012, 34:1453-1458.
261. Raffaghello L., Lee C., Safdie F.M., Wei M., Madia F., Bianchi G., et al. Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy. Proc. Natl. Acad. Sci. U. S. A. 2008, 105:8215-8220.
262. Shi Y., Felley-Bosco E., Marti T.M., Orlowski K., Pruschy M., Stahel R.A. Starvation-induced activation of ATM/Chk2/p53 signaling sensitizes cancer cells to cisplatin. BMC Cancer 2012, 12:571.
263. Safdie F., Brandhorst S., Wei M., Wang W., Lee C., Hwang S., et al. Fasting enhances the response of glioma to chemo- and radiotherapy. PLoS ONE 2012, 7:e44603.
264. Lee C., Raffaghello L., Brandhorst S., Safdie F.M., Bianchi G., Martin-Montalvo A., et al. Fasting cycles retard growth of tumors and sensitize a range of cancer cell types to chemotherapy. Sci. Transl. Med. 2012, 4:124ra27.
265. Seyfried T.N., Mukherjee P. Targeting energy metabolism in brain cancer: review and hypothesis. Nutr. Metab. 2005, 2:30.
266. Longo V.D., Ellerby L.M., Bredesen D.E., Valentine J.S., Gralla E.B. Human Bcl-2 reverses survival defects in yeast lacking superoxide dismutase and delays death of wild-type yeast. J. Cell Biol. 1997, 137:1581-1588.
267. Gonidakis S., Finkel S.E., Longo V.D. Lifespan extension and paraquat resistance in a ubiquinone-deficient Escherichia coli mutant depend on transcription factors ArcA and TdcA. Aging 2011, 3:291-303.
268. Wei M., Fabrizio P., Hu J., Ge H., Cheng C., Li L., et al. Life span extension by calorie restriction depends on Rim15 and transcription factors downstream of Ras/PKA Tor, and Sch9. PLoS Genet. 2008, 4:e13.
269. Wei M., Fabrizio P., Madia F., Hu J., Ge H., Li L.M., et al. Tor1/Sch9-regulated carbon source substitution is as effective as calorie restriction in life span extension. PLoS Genet. 2009, 5:e1000467.
270. Weinkove D., Halstead J.R., Gems D., Divecha N. Long-term starvation and ageing induce AGE-1/PI 3-kinase-dependent translocation of DAF-16/FOXO to the cytoplasm. BMC Biol. 2006, 4:1.
271. Tettweiler G., Miron M., Jenkins M., Sonenberg N., Lasko P.F. Starvation and oxidative stress resistance in Drosophila are mediated through the eIF4E-binding protein, d4E-BP. Genes Dev. 2005, 19:1840-1843.
272. Michalsen A., Riegert M., Ludtke R., Backer M., Langhorst J., Schwickert M., et al. Mediterranean diet or extended fasting's influence on changing the intestinal microflora, immunoglobulin A secretion and clinical outcome in patients with rheumatoid arthritis and fibromyalgia: an observational study. BMC Complement Altern. Med. 2005, 5:22.
273. Goldhamer A., Lisle D., Parpia B., Anderson S.V., Campbell T.C. Medically supervised water-only fasting in the treatment of hypertension. J. Manip. Physiol. Ther. 2001, 24:335-339.
274. Safdie F.M., Dorff T., Quinn D., Fontana L., Wei M., Lee C., et al. Fasting and cancer treatment in humans: a case series report. Aging (Milano) 2009, 1:988-1007.
275. Laviano A., Rossi Fanelli F. Toxicity in chemotherapy - when less is more. N. Engl. J. Med. 2012, 366:2319-2320.
276. Kushi L.H., Doyle C., McCullough M., Rock C.L., Demark-Wahnefried W., Bandera E.V., et al. American Cancer Society Guidelines on nutrition and physical activity for cancer prevention: reducing the risk of cancer with healthy food choices and physical activity. CA Cancer J. Clin. 2012, 62:30-67.
277. Byers T., Nestle M., McTiernan A., Doyle C., Currie-Williams A., Gansler T., et al. American Cancer Society guidelines on nutrition and physical activity for cancer prevention: reducing the risk of cancer with healthy food choices and physical activity. CA Cancer J. Clin. 2002, 52:92-119.
278. Ballard-Barbash R., Friedenreich C.M., Courneya K.S., Siddiqi S.M., McTiernan A., Alfano C.M. Physical activity, biomarkers, and disease outcomes in cancer survivors: a systematic review. J. Natl. Cancer Inst. 2012, 104:815-840.
279. Betof A.S., Dewhirst M.W., Jones L.W. Effects and potential mechanisms of exercise training on cancer progression: a translational perspective. Brain Behav. Immun. 2013, 30(Suppl.):S75-S87.
280. McTiernan A. Mechanisms linking physical activity with cancer. Nat. Rev. Cancer 2008, 8:205-211.
281. Zhu Z., Jiang W., Zacher J.H., Neil E.S., McGinley J.N., Thompson H.J. Effects of energy restriction and wheel running on mammary carcinogenesis and host systemic factors in a rat model. Cancer Prev. Res. (Phila.) 2012, 5:414-422.
282. Jiang W., Zhu Z., Thompson H.J. Effects of limiting energy availability via diet and physical activity on mammalian target of rapamycin-related signaling in rat mammary carcinomas. Carcinogenesis 2013, 34:378-387.
283. Jones L.W., Antonelli J., Masko E.M., Broadwater G., Lascola C.D., Fels D., et al. Exercise modulation of the host-tumor interaction in an orthotopic model of murine prostate cancer. J. Appl. Physiol. 2012, 113:263-272.
284. Jones L.W., Viglianti B.L., Tashjian J.A., Kothadia S.M., Keir S.T., Freedland S.J., et al. Effect of aerobic exercise on tumor physiology in an animal model of human breast cancer. J. Appl. Physiol. 2010, 108:343-348.
285. McTiernan A., Sorensen B., Yasui Y., Tworoger S.S., Ulrich C.M., Irwin M.L., et al. No effect of exercise on insulin-like growth factor 1 and insulin-like growth factor binding protein 3 in postmenopausal women: a 12-month randomized clinical trial. Cancer Epidemiol. Biomark. Prev. 2005, 14:1020-1021.
286. Frank L.L., Sorensen B.E., Yasui Y., Tworoger S.S., Schwartz R.S., Ulrich C.M., et al. Effects of exercise on metabolic risk variables in overweight postmenopausal women: a randomized clinical trial. Obes. Res. 2005, 13:615-625.
287. Fairey A.S., Courneya K.S., Field C.J., Bell G.J., Jones L.W., Mackey J.R. Effects of exercise training on fasting insulin, insulin resistance, insulin-like growth factors, and insulin-like growth factor binding proteins in postmenopausal breast cancer survivors: a randomized controlled trial. Cancer Epidemiol. Biomark. Prev. 2003, 12:721-727.
288. Irwin M.L., McTiernan A., Bernstein L., Gilliland F.D., Baumgartner R., Baumgartner K., et al. Relationship of obesity and physical activity with C-peptide, leptin, and insulin-like growth factors in breast cancer survivors. Cancer Epidemiol. Biomark. Prev. 2005, 14:2881-2888.
289. Schmitz K.H., Ahmed R.L., Hannan P.J., Yee D. Safety and efficacy of weight training in recent breast cancer survivors to alter body composition, insulin, and insulin-like growth factor axis proteins. Cancer Epidemiol. Biomark. Prev. 2005, 14:1672-1680.
290. Janelsins M.C., Davis P.G., Wideman L., Katula J.A., Sprod L.K., Peppone L.J., et al. Effects of Tai Chi Chuan on insulin and cytokine levels in a randomized controlled pilot study on breast cancer survivors. Clin. Breast Cancer 2011, 11:161-170.
291. Ligibel J.A., Campbell N., Partridge A., Chen W.Y., Salinardi T., Chen H., et al. Impact of a mixed strength and endurance exercise intervention on insulin levels in breast cancer survivors. J. Clin. Oncol. 2008, 26:907-912.
292. Irwin M.L., Varma K., Alvarez-Reeves M., Cadmus L., Wiley A., Chung G.G., et al. Randomized controlled trial of aerobic exercise on insulin and insulin-like growth factors in breast cancer survivors: the Yale Exercise and Survivorship study. Cancer Epidemiol. Biomark. Prev. 2009, 18:306-313.
293. Taghian A.G., Abi-Raad R., Assaad S.I., Casty A., Ancukiewicz M., Yeh E., et al. Paclitaxel decreases the interstitial fluid pressure and improves oxygenation in breast cancers in patients treated with neoadjuvant chemotherapy: clinical implications. J. Clin. Oncol. 2005, 23:1951-1961.
294. 2 tension measurements. Cancer Res. 1991, 51:6098-6102.
295. Moon E.J., Brizel D.M., Chi J.T., Dewhirst M.W. The potential role of intrinsic hypoxia markers as prognostic variables in cancer. Antioxid. Redox Signal. 2007, 9:1237-1294.
296. Edwards D.G., Schofield R.S., Lennon S.L., Pierce G.L., Nichols W.W., Braith R.W. Effect of exercise training on endothelial function in men with coronary artery disease. Am. J. Cardiol. 2004, 93:617-620.
297. Hambrecht R., Wolf A., Gielen S., Linke A., Hofer J., Erbs S., et al. Effect of exercise on coronary endothelial function in patients with coronary artery disease. N. Engl. J. Med. 2000, 342:454-460.
298. Allen J.D., Geaghan J.P., Greenway F., Welsch M.A. Time course of improved flow-mediated dilation after short-term exercise training. Med. Sci. Sports Exerc. 2003, 35:847-853.
299. Allen J.D., Welsch M., Aucoin N., Wood R., Lee M., LeBlanc K.E. Forearm vasoreactivity in type 1diabetic subjects. Can. J. Appl. Physiol. 2001, 26:34-43.
300. Hambrecht R., Fiehn E., Weigl C., Gielen S., Hamann C., Kaiser R., et al. Regular physical exercise corrects endothelial dysfunction and improves exercise capacity in patients with chronic heart failure. Circulation 1998, 98:2709-2715.
301. Ostlund R.E., Yang J.W., Klein S., Gingerich R. Relation between plasma leptin concentration and body fat, gender, diet, age, and metabolic covariates. J. Clin. Endocrinol. Metab. 1996, 81:3909-3913.
302. Hu E., Liang P., Spiegelman B.M. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J. Biol. Chem. 1996, 271:10697-10703.
303. Wellen K.E., Hotamisligil G.S. Obesity-induced inflammatory changes in adipose tissue. J. Clin. Invest. 2003, 112:1785-1788.
304. Yildiz B.O., Suchard M.A., Wong M.L., McCann S.M., Licinio J. Alterations in the dynamics of circulating ghrelin, adiponectin, and leptin in human obesity. Proc. Natl. Acad. Sci. U. S. A. 2004, 101:10434-10439.
305. Research WCRFAIfC Food Nutrition Physical Activity, and the Prevention of Cancer: A Global Perspective 2007, AICR, Washington DC.
306. Calle E.E., Rodriguez C., Walker-Thurmond K., Thun M.J. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N. Engl. J. Med. 2003, 348:1625-1638.
307. Colditz G.A., Wolin K.Y., Gehlert S. Applying what we know to accelerate cancer prevention. Sci. Transl. Med. 2012, 4:127rv4.
308. Calle E.E., Kaaks R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat. Rev. Cancer 2004, 4:579-591.
309. Hursting S.D., Dunlap S.M. Obesity, metabolic dysregulation, and cancer: a growing concern and an inflammatory (and microenvironmental) issue. Ann. N. Y. Acad. Sci. 2012, 1271:82-87.
310. Vucenik I., Stains J.P. Obesity and cancer risk: evidence, mechanisms, and recommendations. Ann. N. Y. Acad. Sci. 2012, 1271:37-43.
311. Pollak M.N. Investigating metformin for cancer prevention and treatment: the end of the beginning. Cancer Discov. 2012, 2:778-790.
312. Sankaranarayanapillai M., Zhang N., Baggerly K.A., Gelovani J.G. Metabolic shifts induced by fatty acid synthase inhibitor orlistat in non-small cell lung carcinoma cells provide novel pharmacodynamic biomarkers for positron emission tomography and magnetic resonance spectroscopy. Mol. Imag. Biol. 2013, 15:136-147.
313. Luengo A., Sullivan L.B., Heiden M.G. Understanding the complex-I-ty of metformin action: limiting mitochondrial respiration to improve cancer therapy. BMC Biol. 2014, 12:82.
314. Madhok B.M., Yeluri S., Perry S.L., Hughes T.A., Jayne D.G. Targeting glucose metabolism: an emerging concept for anticancer therapy. Am. J. Clin. Oncol. 2011, 34:628-635.
315. Jacobs S.R., Herman C.E., Maciver N.J., Wofford J.A., Wieman H.L., Hammen J.J., et al. Glucose uptake is limiting in T cell activation and requires CD28-mediated Akt-dependent and independent pathways. J. Immunol. 2008, 180:4476-4486.
316. Delgoffe G.M., Kole T.P., Zheng Y., Zarek P.E., Matthews K.L., Xiao B., et al. The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment. Immunity 2009, 30:832-844.
317. Michalek R.D., Gerriets V.A., Jacobs S.R., Macintyre A.N., Maciver N.J., Mason E.F., et al. Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. J. Immunol. 2011, 186:3299-3303.
318. Shi L.Z., Wang R., Huang G., Vogel P., Neale G., Green D.R., et al. HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J. Exp. Med. 2011, 208:1367-1376.
319. Pearce E.L., Walsh M.C., Cejas P.J., Harms G.M., Shen H., Wang L.S., et al. Enhancing CD8 T-cell memory by modulating fatty acid metabolism. Nature 2009, 460:103-107.
320. van der Windt G.J., Everts B., Chang C.H., Curtis J.D., Freitas T.C., Amiel E., et al. Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development. Immunity 2012, 36:68-78.
321. Harjes U., Bensaad K., Harris A.L. Endothelial cell metabolism and implications for cancer therapy. Br. J. Cancer 2012, 107:1207-1212.
322. Chiong M., Morales P., Torres G., Gutierrez T., Garcia L., Ibacache M., et al. Influence of glucose metabolism on vascular smooth muscle cell proliferation. VASA Zeitschrift fur Gefasskrankheiten 2013, 42:8-16.
323. Ostroukhova M., Goplen N., Karim M.Z., Michalec L., Guo L., Liang Q., et al. The role of low-level lactate production in airway inflammation in asthma. Am. J. Physiol. Lung Cell. Mol. Physiol. 2012, 302:L300-L307.
324. Raff M.C. Social controls on cell survival and cell death. Nature 1992, 356:397-400.
325. Ward Patrick S., Thompson, Craig B. Metabolic reprogramming: a cancer hallmark even Warburg did not anticipate. Cancer Cell 2012, 21:297-308.
326. Panopoulos A.D., Yanes O., Ruiz S., Kida Y.S., Diep D., Tautenhahn R., et al. The metabolome of induced pluripotent stem cells reveals metabolic changes occurring in somatic cell reprogramming. Cell Res. 2012, 22:168-177.
327. Rathmell J.C., Vander Heiden M.G., Harris M.H., Frauwirth K.A., Thompson C.B. In the absence of extrinsic signals, nutrient utilization by lymphocytes is insufficient to maintain either cell size or viability. Mol. Cell 2000, 6:683-692.
328. Nicholson J.K., Holmes E., Kinross J.M., Darzi A.W., Takats Z., Lindon J.C. Metabolic phenotyping in clinical and surgical environments. Nature 2012, 491:384-392.
329. Tennant D.A., Duran R.V., Gottlieb E. Targeting metabolic transformation for cancer therapy. Nat. Rev. Cancer 2010, 10:267-277.