Insulin enhances metabolic capacities of cancer cells by dual regulation of glycolytic enzyme pyruvate kinase M2

Molecular Cancer

Volumn 12, Issue 1, 2013, Pages

  Iqbal, Mohd Askandar ^a   Siddiqui, Farid Ahmad ^a   Gupta, Vibhor ^a   Chattopadhyay, Shilpi ^a   Gopinath, Prakasam ^a   Kumar, Bhupender ^a   Manvati, Siddharth ^a   Chaman, Noor ^a   Bamezai, Rameshwar N K ^a  

^a JAWAHARLAL NEHRU UNIVERSITY   (India)

Author keywords

Cancer; Glycolysis; HepG2; Insulin; Lactate; Metabolism; PKM2

Indexed keywords

COBALT CHLORIDE; HYPOXIA INDUCIBLE FACTOR 1ALPHA; INSULIN; PHOSPHATIDYLINOSITOL 3 KINASE; PYRUVATE KINASE; PYRUVATE KINASE M2; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; SMALL INTERFERING RNA; UNCLASSIFIED DRUG;

ARTICLE; CANCER CELL; CANCER GROWTH; DENSITY GRADIENT CENTRIFUGATION; ENZYME ACTIVITY; ENZYME PHOSPHORYLATION; ENZYME REGULATION; GLYCOLYSIS; INSULIN TREATMENT; METABOLIC CAPACITY; PROTEIN EXPRESSION; PROTEIN SUBUNIT; SIGNAL TRANSDUCTION; UPREGULATION;

CELL LINE, TUMOR; ENZYME ACTIVATION; GENE EXPRESSION REGULATION, NEOPLASTIC; GLYCOLYSIS; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; INSULIN; ISOENZYMES; MODELS, BIOLOGICAL; NADP; NEOPLASMS; PHOSPHATIDYLINOSITOL 3-KINASES; PROTEIN SUBUNITS; PYRUVATE KINASE; REACTIVE OXYGEN SPECIES; TOR SERINE-THREONINE KINASES;

EID: 84880000375     PISSN: None     EISSN: 14764598     Source Type: Journal    
DOI: 10.1186/1476-4598-12-72     Document Type: Article

References (51)

1. Warburg O. On the origin of cancer cells. Science 1956, 123:309-314. 10.1126/science.123.3191.309, 13298683.
2. Weber WA, Avril N, Schwaiger M. Relevance of positron emission tomography (PET) in oncology. Strahlenther Onkol 1999, 175:356-373. 10.1007/s000660050022, 10481766.
3. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 2009, 324:1029-1033. 10.1126/science.1160809, 2849637, 19460998.
4. Gatenby RA, Gillies RJ. Why do cancers have high aerobic glycolysis?. Nat Rev Cancer 2004, 4:891-899. 10.1038/nrc1478, 15516961.
5. Tennant DA, Duran RV, Gottlieb E. Targeting metabolic transformation for cancer therapy. Nat Rev Cancer 2010, 10:267-277. 10.1038/nrc2817, 20300106.
6. Vander Heiden MG. Targeting cancer metabolism: a therapeutic window opens. Nat Rev Drug Discov 2011, 10:671-684. 10.1038/nrd3504, 21878982.
7. Majumder PK, Febbo PG, Bikoff R, Berger R, Xue Q, McMahon LM, Manola J, Brugarolas J, McDonnell TJ, Golub TR, et al. mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways. Nat Med 2004, 10:594-601. 10.1038/nm1052, 15156201.
8. Lv L, Li D, Zhao D, Lin R, Chu Y, Zhang H, Zha Z, Liu Y, Li Z, Xu Y, et al. Acetylation targets the M2 isoform of pyruvate kinase for degradation through chaperone-mediated autophagy and promotes tumor growth. Mol Cell 2011, 42:719-730. 10.1016/j.molcel.2011.04.025, 21700219.
9. Deberardinis RJ, Sayed N, Ditsworth D, Thompson CB. Brick by brick: metabolism and tumor cell growth. Curr Opin Genet Dev 2008, 18:54-61. 10.1016/j.gde.2008.02.003, 2476215, 18387799.
10. Gupta V, Bamezai RN. Human pyruvate kinase M2: a multifunctional protein. Protein Sci 2010, 19:2031-2044. 10.1002/pro.505, 3005776, 20857498.
11. Mazurek S, Boschek CB, Hugo F, Eigenbrodt E. Pyruvate kinase type M2 and its role in tumor growth and spreading. Semin Cancer Biol 2005, 15:300-308. 10.1016/j.semcancer.2005.04.009, 15908230.
12. Christofk HR, Vander Heiden MG, Harris MH, Ramanathan A, Gerszten RE, Wei R, Fleming MD, Schreiber SL, Cantley LC. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature 2008, 452:230-233. 10.1038/nature06734, 18337823.
13. Christofk HR, Vander Heiden MG, Wu N, Asara JM, Cantley LC. Pyruvate kinase M2 is a phosphotyrosine-binding protein. Nature 2008, 452:181-186. 10.1038/nature06667, 18337815.
14. Mazurek S, Michel A, Eigenbrodt E. Effect of extracellular AMP on cell proliferation and metabolism of breast cancer cell lines with high and low glycolytic rates. J Biol Chem 1997, 272:4941-4952. 10.1074/jbc.272.8.4941, 9030554.
15. Zwerschke W, Mazurek S, Massimi P, Banks L, Eigenbrodt E, Jansen-Durr P. Modulation of type M2 pyruvate kinase activity by the human papillomavirus type 16 E7 oncoprotein. Proc Natl Acad Sci USA 1999, 96:1291-1296. 10.1073/pnas.96.4.1291, 15456, 9990017.
16. Gupta V, Kalaiarasan P, Faheem M, Singh N, Iqbal MA, Bamezai RN. Dominant negative mutations affect oligomerization of human pyruvate kinase M2 isozyme and promote cellular growth and polyploidy. J Biol Chem 2010, 285:16864-16873. 10.1074/jbc.M109.065029, 2878009, 20304929.
17. Gallagher EJ, LeRoith D. Minireview: IGF, Insulin, and Cancer. Endocrinology 2011, 152:2546-2551. 10.1210/en.2011-0231, 21540285.
18. Szabolcs M, Keniry M, Simpson L, Reid LJ, Koujak S, Schiff SC, Davidian G, Licata S, Gruvberger-Saal S, Murty VV, et al. Irs2 inactivation suppresses tumor progression in Pten+/- mice. Am J Pathol 2009, 174:276-286. 10.2353/ajpath.2009.080086, 2631340, 19095950.
19. Zhang H, Fagan DH, Zeng X, Freeman KT, Sachdev D, Yee D. Inhibition of cancer cell proliferation and metastasis by insulin receptor down-regulaion. Oncogene 2010, 29:2517-2527. 10.1038/onc.2010.17, 2861724, 20154728.
20. Fierz Y, Novosyadlyy R, Vijayakumar A, Yakar S, LeRoith D. Insulin-sensitizing therapy attenuates type 2 diabetes-mediated mammary tumor progression. Diabetes 2010, 59:686-693. 10.2337/db09-1291, 2828655, 19959755.
21. Hemkens LG, Grouven U, Bender R, Gunster C, Gutschmidt S, Selke GW, Sawicki PT. Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues: a cohort study. Diabetologia 2009, 52:1732-1744. 10.1007/s00125-009-1418-4, 2723679, 19565214.
22. Hemminki K, Li X, Sundquist J, Sundquist K. Risk of cancer following hospitalization for type 2 diabetes. Oncologist 2010, 15:548-555. 10.1634/theoncologist.2009-0300, 3227990, 20479278.
23. Coughlin SS, Calle EE, Teras LR, Petrelli J, Thun MJ. Diabetes mellitus as a predictor of cancer mortality in a large cohort of US adults. Am J Epidemiol 2004, 159:1160-1167. 10.1093/aje/kwh161, 15191933.
24. Balkau B, Kahn HS, Courbon D, Eschwege E, Ducimetiere P. Hyperinsulinemia predicts fatal liver cancer but is inversely associated with fatal cancer at some other sites: the paris prospective study. Diabetes Care 2001, 24:843-849. 10.2337/diacare.24.5.843, 11347741.
25. Ulanet DB, Ludwig DL, Kahn CR, Hanahan D. Insulin receptor functionally enhances multistage tumor progression and conveys intrinsic resistance to IGF-1R targeted therapy. Proc Natl Acad Sci USA 2010, 107:10791-10798. 10.1073/pnas.0914076107, 2890766, 20457905.
26. Lee JW, Soung YH, Kim SY, Lee HW, Park WS, Nam SW, Kim SH, Lee JY, Yoo NJ, Lee SH. PIK3CA gene is frequently mutated in breast carcinomas and hepatocellular carcinomas. Oncogene 2005, 24:1477-1480. 10.1038/sj.onc.1208304, 15608678.
27. Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, Yan H, Gazdar A, Powell SM, Riggins GJ, et al. High frequency of mutations of the PIK3CA gene in human cancers. Science 2004, 304:554. 10.1126/science.1096502, 15016963.
28. Taniguchi CM, Tran TT, Kondo T, Luo J, Ueki K, Cantley LC, Kahn CR. Phosphoinositide 3-kinase regulatory subunit p85alpha suppresses insulin action via positive regulation of PTEN. Proc Natl Acad Sci USA 2006, 103:12093-12097. 10.1073/pnas.0604628103, 1524929, 16880400.
29. Luo W, Hu H, Chang R, Zhong J, Knabel M, O'Meally R, Cole RN, Pandey A, Semenza GL. Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1. Cell 2011, 145:732-744. 10.1016/j.cell.2011.03.054, 3130564, 21620138.
30. Sun Q, Chen X, Ma J, Peng H, Wang F, Zha X, Wang Y, Jing Y, Yang H, Chen R, et al. Mammalian target of rapamycin up-regulation of pyruvate kinase isoenzyme type M2 is critical for aerobic glycolysis and tumor growth. Proc Natl Acad Sci USA 2011, 108:4129-4134. 10.1073/pnas.1014769108, 3054028, 21325052.
31. Treins C, Giorgetti-Peraldi S, Murdaca J, Semenza GL, Van Obberghen E. Insulin stimulates hypoxia-inducible factor 1 through a phosphatidylinositol 3-kinase/target of rapamycin-dependent signaling pathway. J Biol Chem 2002, 277:27975-27981. 10.1074/jbc.M204152200, 12032158.
32. Piret JP, Mottet D, Raes M, Michiels C. CoCl2, a chemical inducer of hypoxia-inducible factor-1, and hypoxia reduce apoptotic cell death in hepatoma cell line HepG2. Ann N Y Acad Sci 2002, 973:443-447. 10.1111/j.1749-6632.2002.tb04680.x, 12485908.
33. Hitosugi T, Kang S, Vander Heiden MG, Chung TW, Elf S, Lythgoe K, Dong S, Lonial S, Wang X, Chen GZ, et al. Tyrosine phosphorylation inhibits PKM2 to promote the Warburg effect and tumor growth. Sci Signal 2009, 2:ra73. 10.1126/scisignal.2000431, 2812789, 19920251.
34. Anastasiou D, Poulogiannis G, Asara JM, Boxer MB, Jiang JK, Shen M, Bellinger G, Sasaki AT, Locasale JW, Auld DS, et al. Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses. Science 2011, 334:1278-1283. 10.1126/science.1211485, 3471535, 22052977.
35. Lad PM, Hammes GG. Physical and chemical properties of rabbit muscle phosphofructokinase cross-linked with dimethyl suberimidate. Biochemistry 1974, 13:4530-4537. 10.1021/bi00719a009, 4371809.
36. Erkekoglu P, Baydar T. Evaluation of the protective effect of ascorbic acid on nitrite- and nitrosamine-induced cytotoxicity and genotoxicity in human hepatoma line. Toxicol Mech Methods 2010, 20:45-52. 10.3109/15376510903583711, 20100056.
37. Frei B. Ascorbic acid protects lipids in human plasma and low-density lipoprotein against oxidative damage. Am J Clin Nutr 1991, 54:1113S-1118S.
38. Dasgupta S, Hoque MO, Upadhyay S, Sidransky D. Mitochondrial cytochrome B gene mutation promotes tumor growth in bladder cancer. Cancer Res 2008, 68:700-706. 10.1158/0008-5472.CAN-07-5532, 18245469.
39. Macip S, Igarashi M, Fang L, Chen A, Pan ZQ, Lee SW, Aaronson SA. Inhibition of p21-mediated ROS accumulation can rescue p21-induced senescence. EMBO J 2002, 21:2180-2188. 10.1093/emboj/21.9.2180, 125979, 11980715.
40. Staal FJ, Roederer M, Herzenberg LA. Intracellular thiols regulate activation of nuclear factor kappa B and transcription of human immunodeficiency virus. Proc Natl Acad Sci USA 1990, 87:9943-9947. 10.1073/pnas.87.24.9943, 55290, 2263644.
41. Kattan Z, Minig V, Leroy P, Dauca M, Becuwe P. Role of manganese superoxide dismutase on growth and invasive properties of human estrogen-independent breast cancer cells. Breast Cancer Res Treat 2008, 108:203-215. 10.1007/s10549-007-9597-5, 17473980.
42. Pankratz SL, Tan EY, Fine Y, Mercurio AM, Shaw LM. Insulin receptor substrate-2 regulates aerobic glycolysis in mouse mammary tumor cells via glucose transporter 1. J Biol Chem 2009, 284:2031-2037. 2629099, 19056742.
43. Elstrom RL, Bauer DE, Buzzai M, Karnauskas R, Harris MH, Plas DR, Zhuang H, Cinalli RM, Alavi A, Rudin CM, Thompson CB. Akt stimulates aerobic glycolysis in cancer cells. Cancer Res 2004, 64:3892-3899. 10.1158/0008-5472.CAN-03-2904, 15172999.
44. Iqbal MA, Bamezai RNK. Resveratrol inhibits Cancer cell metabolism by down regulating pyruvate kinase M2 via inhibition of mammalian target of rapamycin. PLoS One 2012, 7:e36764. 10.1371/journal.pone.0036764, 3344940, 22574221.
45. Cairns RA, Harris IS, Mak TW. Regulation of cancer cell metabolism. Nat Rev Cancer 2011, 11:85-95.
46. Bluemlein K, Gruning NM, Feichtinger RG, 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. 3248187, 21789790.
47. Asai Y, Yamada K, Watanabe T, Keng VW, Noguchi T. Insulin stimulates expression of the pyruvate kinase M gene in 3T3-L1 adipocytes. Biosci Biotechnol Biochem 2003, 67:1272-1277. 10.1271/bbb.67.1272, 12843653.
48. Komazawa N, Matsuda M, Kondoh G, Mizunoya W, Iwaki M, Takagi T, Sumikawa Y, Inoue K, Suzuki A, Mak TW, et al. Enhanced insulin sensitivity, energy expenditure and thermogenesis in adipose-specific Pten suppression in mice. Nat Med 2004, 10:1208-1215. 10.1038/nm1117, 15489860.
49. Panasyuk G, Espeillac C, Chauvin C, Pradelli LA, Horie Y, Suzuki A, Annicotte JS, Fajas L, Foretz M, Verdeguer F, et al. PPARgamma contributes to PKM2 and HK2 expression in fatty liver. Nat Commun 2012, 3:672. 3293420, 22334075.
50. Hsu IR, Kim SP, Kabir M, Bergman RN. Metabolic syndrome, hyperinsulinemia, and cancer. Am J Clin Nutr 2007, 86:s867-s871.
51. Ryu H, Walker JK, Kim S, Koo N, Barak LS, Noguchi T, Kang BY, Kim KM. Regulation of M2-type pyruvate kinase mediated by the high-affinity IgE receptors is required for mast cell degranulation. Br J Pharmacol 2008, 154:1035-1046. 10.1038/bjp.2008.148, 2451040, 18587448.