The glycolytic shift in fumarate-hydratase-deficient kidney cancer lowers AMPK levels, increases anabolic propensities and lowers cellular iron levels

Cancer Cell

Volumn 20, Issue 3, 2011, Pages 315-327

  Tong, Wing Hang ^a   Sourbier, Carole ^b   Kovtunovych, Gennady ^a   Jeong, Suh Young ^a   Vira, Manish ^c   Ghosh, Manik ^a   Romero, Vladimir Valera ^b   Sougrat, Rachid ^d   Vaulont, Sophie ^e   Viollet, Benoit ^e   Kim, Yeong Sang ^b   Lee, Sunmin ^b   Trepel, Jane ^b   Srinivasan, Ramaprasad ^b   Bratslavsky, Gennady ^b   Yang, Youfeng ^b   Linehan, W Marston ^b   Rouault, Tracey A ^a  

^a EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT   (United States)

^b NATIONAL CANCER INSTITUTE   (United States)

^c ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

^d KING ABDULLAH UNIVERSITY OF SCIENCE AND TECHNOLOGY   (Saudi Arabia)

^e INSTITUT COCHIN   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYL COENZYME A CARBOXYLASE; FUMARATE HYDRATASE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; HYPOXIA INDUCIBLE FACTOR 1ALPHA; IRON; IRON REGULATORY PROTEIN 1; IRON REGULATORY PROTEIN 2; NATURAL RESISTANCE ASSOCIATED MACROPHAGE PROTEIN 2; PROTEIN P53; PROTEIN S6;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BIOSYNTHESIS; CANCER CELL CULTURE; CANCER GROWTH; CELL LEVEL; CONTROLLED STUDY; ENZYME ACTIVATION; ENZYME DEFICIENCY; ENZYME INACTIVATION; GENE SILENCING; GENETIC DISORDER; GLYCOLYSIS; HUMAN; HUMAN CELL; HUMAN TISSUE; IRON BLOOD LEVEL; IRON DEFICIENCY; KIDNEY CANCER; LEIOMYOMATOSIS; METABOLIC REGULATION; MOUSE; MUTATION; NONHUMAN; PRIORITY JOURNAL; PROPENSITY SCORE; PROTEIN EXPRESSION; TUMOR SUPPRESSOR GENE;

EID: 80052572942     PISSN: 15356108     EISSN: 18783686     Source Type: Journal    
DOI: 10.1016/j.ccr.2011.07.018     Document Type: Article

References (61)

1. Bayley J.P., Devilee P. Warburg tumours and the mechanisms of mitochondrial tumour suppressor genes. Barking up the right tree?. Curr. Opin. Genet. Dev. 2010, 20:324-329.
2. Baysal B.E., Ferrell R.E., Willett-Brozick J.E., Lawrence E.C., Myssiorek D., Bosch A., van der Mey A., Taschner P.E., Rubinstein W.S., Myers E.N., et al. Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science 2000, 287:848-851.
3. Bruick R.K., McKnight S.L. A conserved family of prolyl-4-hydroxylases that modify HIF. Science 2001, 294:1337-1340.
4. Buzzai M., Jones R.G., Amaravadi R.K., Lum J.J., DeBerardinis R.J., Zhao F., Viollet B., Thompson C.B. Systemic treatment with the antidiabetic drug metformin selectively impairs p53-deficient tumor cell growth. Cancer Res. 2007, 67:6745-6752.
5. Chen J., Zhao S., Nakada K., Kuge Y., Tamaki N., Okada F., Wang J., Shindo M., Higashino F., Takeda K., et al. Dominant-negative hypoxia-inducible factor-1 alpha reduces tumorigenicity of pancreatic cancer cells through the suppression of glucose metabolism. Am. J. Pathol. 2003, 162:1283-1291.
6. Dang D.T., Chen F., Gardner L.B., Cummins J.M., Rago C., Bunz F., Kantsevoy S.V., Dang L.H. Hypoxia-inducible factor-1alpha promotes nonhypoxia-mediated proliferation in colon cancer cells and xenografts. Cancer Res. 2006, 66:1684-1936.
7. 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.
8. Elstrom R.L., Bauer D.E., Buzzai M., Karnauskas R., Harris M.H., Plas D.R., Zhuang H., Cinalli R.M., Alavi A., Rudin C.M., Thompson C.B. Akt stimulates aerobic glycolysis in cancer cells. Cancer Res. 2004, 64:3892-3899.
9. Epstein A.C., Gleadle J.M., McNeill L.A., Hewitson K.S., O'Rourke J., Mole D.R., Mukherji M., Metzen E., Wilson M.I., Dhanda A., et al. C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell 2001, 107:43-54.
10. Evans J.M., Donnelly L.A., Emslie-Smith A.M., Alessi D.R., Morris A.D. Metformin and reduced risk of cancer in diabetic patients. BMJ 2005, 330:1304-1305.
11. Gordan J.D., Simon M.C. Hypoxia-inducible factors: central regulators of the tumor phenotype. Curr. Opin. Genet. Dev. 2007, 17:71-77.
12. Haase V.H. Hypoxic regulation of erythropoiesis and iron metabolism. Am. J. Physiol. Renal Physiol. 2010, 299:F1-F13.
13. Hadad S.M., Baker L., Quinlan P.R., Robertson K.E., Bray S.E., Thomson G., Kellock D., Jordan L.B., Purdie C.A., Hardie D.G., et al. Histological evaluation of AMPK signalling in primary breast cancer. BMC Cancer 2009, 9:307.
14. Hao H.X., Khalimonchuk O., Schraders M., Dephoure N., Bayley J.P., Kunst H., Devilee P., Cremers C.W., Schiffman J.D., Bentz B.G., et al. SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma. Science 2009, 325:1139-1142.
15. Hardie D.G. AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat. Rev. Mol. Cell Biol. 2007, 8:774-785.
16. Haurie V., Boucherie H., Sagliocco F. The Snf1 protein kinase controls the induction of genes of the iron uptake pathway at the diauxic shift in Saccharomyces cerevisiae. J. Biol. Chem. 2003, 278:45391-45396.
17. Hirsch H.A., Iliopoulos D., Tsichlis P.N., Struhl K. Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission. Cancer Res. 2009, 69:7507-7511.
18. Imamura K., Ogura T., Kishimoto A., Kaminishi M., Esumi H. Cell cycle regulation via p53 phosphorylation by a 5'-AMP activated protein kinase activator, 5-aminoimidazole- 4-carboxamide-1-beta-D-ribofuranoside, in a human hepatocellular carcinoma cell line. Biochem. Biophys. Res. Commun. 2001, 287:562-567.
19. Inoki K., Guan K.L. Tuberous sclerosis complex, implication from a rare genetic disease to common cancer treatment. Hum. Mol. Genet. 2009, 18(R1):R94-R100.
20. Isaacs J.S., Jung Y.J., Mole D.R., Lee S., Torres-Cabala C., Chung Y.L., Merino M., Trepel J., Zbar B., Toro J., et al. HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: novel role of fumarate in regulation of HIF stability. Cancer Cell 2005, 8:143-153.
21. Jones R.G., Plas D.R., Kubek S., Buzzai M., Mu J., Xu Y., Birnbaum M.J., Thompson C.B. AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Mol. Cell 2005, 18:283-293.
22. Jones R.G., Thompson C.B. Tumor suppressors and cell metabolism: a recipe for cancer growth. Genes Dev. 2009, 23:537-548.
23. Kaelin W.G., Ratcliffe P.J. Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol. Cell 2008, 30:393-402.
24. Kaelin W.G., Thompson C.B. Q&A: Cancer: clues from cell metabolism. Nature 2010, 465:562-564.
25. King A., Selak M.A., Gottlieb E. Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer. Oncogene 2006, 25:4675-4682.
26. Kondo K., Klco J., Nakamura E., Lechpammer M., Kaelin W.G. Inhibition of HIF is necessary for tumor suppression by the von Hippel-Lindau protein. Cancer Cell 2002, 1:237-246.
27. Laderoute K.R., Amin K., Calaoagan J.M., Knapp M., Le T., Orduna J., Foretz M., Viollet B. 5'-AMP-activated protein kinase (AMPK) is induced by low-oxygen and glucose deprivation conditions found in solid-tumor microenvironments. Mol. Cell. Biol. 2006, 26:5336-5347.
28. Launonen V., Vierimaa O., Kiuru M., Isola J., Roth S., Pukkala E., Sistonen P., Herva R., Aaltonen L.A. Inherited susceptibility to uterine leiomyomas and renal cell cancer. Proc. Natl. Acad. Sci. USA 2001, 98:3387-3392.
29. LaVaute T., Smith S., Cooperman S., Iwai K., Land W., Meyron-Holtz E., Drake S.K., Miller G., Abu-Asab M., Tsokos M., et al. Targeted deletion of the gene encoding iron regulatory protein-2 causes misregulation of iron metabolism and neurodegenerative disease in mice. Nat. Genet. 2001, 27:209-214.
30. Luo Z., Saha A.K., Xiang X., Ruderman N.B. AMPK, the metabolic syndrome and cancer. Trends Pharmacol. Sci. 2005, 26:69-76.
31. Maffettone C., Chen G., Drozdov I., Ouzounis C., Pantopoulos K. Tumorigenic properties of iron regulatory protein 2 (IRP2) mediated by its specific 73-amino acids insert. PLoS ONE 2010, 5:e10163.
32. Maranchie J.K., Vasselli J.R., Riss J., Bonifacino J.S., Linehan W.M., Klausner R.D. The contribution of VHL substrate binding and HIF1-alpha to the phenotype of VHL loss in renal cell carcinoma. Cancer Cell 2002, 1:247-255.
33. Marsin A.S., Bertrand L., Rider M.H., Deprez J., Beauloye C., Vincent M.F., Van den Berghe G., Carling D., Hue L. Phosphorylation and activation of heart PFK-2 by AMPK has a role in the stimulation of glycolysis during ischaemia. Curr. Biol. 2000, 10:1247-1255.
34. Menendez J.A., Lupu R. Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat. Rev. Cancer 2007, 7:763-777.
35. Merino M.J., Torres-Cabala C., Pinto P., Linehan W.M. The morphologic spectrum of kidney tumors in hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. Am. J. Surg. Pathol. 2007, 31:1578-1585.
36. Mims M.P., Prchal J.T. Divalent metal transporter 1. Hematology 2005, 10:339-345.
37. Muckenthaler M.U., Galy B., Hentze M.W. Systemic iron homeostasis and the iron-responsive element/iron-regulatory protein (IRE/IRP) regulatory network. Annu. Rev. Nutr. 2008, 28:197-213.
38. Musi N., Hayashi T., Fujii N., Hirshman M.F., Witters L.A., Goodyear L.J. AMP-activated protein kinase activity and glucose uptake in rat skeletal muscle. Am. J. Physiol. Endocrinol. Metab. 2001, 280:E677-E684.
39. Pollard P.J., Brière J.J., Alam N.A., Barwell J., Barclay E., Wortham N.C., Hunt T., Mitchell M., Olpin S., Moat S.J., 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, 14:2231-2239.
40. Pollard P.J., Spencer-Dene B., Shukla D., Howarth K., Nye E., El-Bahrawy M., Deheragoda M., Joannou M., McDonald S., Martin A., et al. Targeted inactivation of fh1 causes proliferative renal cyst development and activation of the hypoxia pathway. Cancer Cell 2007, 11:311-319.
41. Puig S., Vergara S.V., Thiele D.J. Cooperation of two mRNA-binding proteins drives metabolic adaptation to iron deficiency. Cell Metab. 2008, 7:555-564.
42. Raval R.R., Lau K.W., Tran M.G., Sowter H.M., Mandriota S.J., Li J.L., Pugh C.W., Maxwell P.H., Harris A.L., Ratcliffe P.J. Contrasting properties of hypoxia-inducible factor 1 (HIF-1) and HIF-2 in von Hippel-Lindau-associated renal cell carcinoma. Mol. Cell. Biol. 2005, 25:5675-5686.
43. Rouault T.A. The role of iron regulatory proteins in mammalian iron homeostasis and disease. Nat. Chem. Biol. 2006, 2:406-414.
44. Sanchez M., Galy B., Muckenthaler M.U., Hentze M.W. Iron-regulatory proteins limit hypoxia-inducible factor-2alpha expression in iron deficiency. Nat. Struct. Mol. Biol. 2007, 14:420-426.
45. Semenza G.L. Regulation of cancer cell metabolism by hypoxia-inducible factor 1. Semin. Cancer Biol. 2009, 19:12-16.
46. Shaw R.J. Glucose metabolism and cancer. Curr. Opin. Cell Biol. 2006, 18:598-608.
47. Sudarshan S., Sourbier C., Kong H.S., Block K., Valera Romero V.A., Yang Y., Galindo C., Mollapour M., Scroggins B., Goode N., et al. Fumarate hydratase deficiency in renal cancer induces glycolytic addiction and hypoxia-inducible transcription factor 1alpha stabilization by glucose-dependent generation of reactive oxygen species. Mol. Cell. Biol. 2009, 29:4080-4090.
48. Sun F., Huo X., Zhai Y., Wang A., Xu J., Su D., Bartlam M., Rao Z. Crystal structure of mitochondrial respiratory membrane protein complex II. Cell 2005, 121:1043-1057.
49. Tabuchi M., Tanaka N., Nishida-Kitayama J., Ohno H., Kishi F. Alternative splicing regulates the subcellular localization of divalent metal transporter 1 isoforms. Mol. Biol. Cell 2002, 13:4371-4387.
50. Tomlinson I.P., Alam N.A., Rowan A.J., Barclay E., Jaeger E.E., Kelsell D., Leigh I., Gorman P., Lamlum H., Rahman S., et al. Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nat. Genet. 2002, 30:406-410. Multiple Leiomyoma Consortium.
51. Toro J.R., Nickerson M.L., Wei M.H., Warren M.B., Glenn G.M., Turner M.L., Stewart L., Duray P., Tourre O., Sharma N., et al. Mutations in the fumarate hydratase gene cause hereditary leiomyomatosis and renal cell cancer in families in North America. Am. J. Hum. Genet. 2003, 73:95-106.
52. Tsuji Y., Akebi N., Lam T.K., Nakabeppu Y., Torti S.V., Torti F.M. FER-1, an enhancer of the ferritin H gene and a target of E1A-mediated transcriptional repression. Mol. Cell. Biol. 1995, 15:5152-5164.
53. 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.
54. Vousden K.H., Ryan K.M. p53 and metabolism. Nat. Rev. Cancer 2009, 9:691-700.
55. Warburg O. On the origin of cancer cells. Science 1956, 123:309-314.
56. Wu K.J., Polack A., Dalla-Favera R. Coordinated regulation of iron-controlling genes, H-ferritin and IRP2, by c-MYC. Science 1999, 283:676-679.
57. Xiang X., Saha A.K., Wen R., Ruderman N.B., Luo Z. AMP-activated protein kinase activators can inhibit the growth of prostate cancer cells by multiple mechanisms. Biochem. Biophys. Res. Commun. 2004, 321:161-167.
58. Yang Y., Valera V.A., Padilla-Nash H.M., Sourbier C., Vocke C.D., Vira M.A., Abu-Asab M.S., Bratslavsky G., Tsokos M., Merino M.J., et al. UOK 262 cell line, fumarate hydratase deficient (FH-/FH-) hereditary leiomyomatosis renal cell carcinoma: in vitro and in vivo model of an aberrant energy metabolic pathway in human cancer. Cancer Genet. Cytogenet. 2010, 196:45-55.
59. Zhang F., Wang W., Tsuji Y., Torti S.V., Torti F.M. Post-transcriptional modulation of iron homeostasis during p53-dependent growth arrest. J. Biol. Chem. 2008, 283:33911-33918.
60. Zhang H., Cicchetti G., Onda H., Koon H.B., Asrican K., Bajraszewski N., Vazquez F., Carpenter C.L., Kwiatkowski D.J. Loss of Tsc1/Tsc2 activates mTOR and disrupts PI3K-Akt signaling through downregulation of PDGFR. J. Clin. Invest. 2003, 112:1223-1233.
61. Zimmer M., Ebert B.L., Neil C., Brenner K., Papaioannou I., Melas A., Tolliday N., Lamb J., Pantopoulos K., Golub T., Iliopoulos O. Small-molecule inhibitors of HIF-2a translation link its 5'UTR iron-responsive element to oxygen sensing. Mol. Cell 2008, 32:838-848.