Tumor Cell Metabolism: Cancer's Achilles' Heel

Cancer Cell

Volumn 13, Issue 6, 2008, Pages 472-482

  Kroemer, Guido ^a,b,c   Pouyssegur, Jacques ^d  

^a INSERM   (France)

^b INSTITUT GUSTAVE ROUSSY   (France)

^c UNIVERSITÉ PARIS SACLAY   (France)

^d CENTRE DE BIOCHIMIE   (France)

Author keywords

[No Author keywords available]

Indexed keywords

APOPTOSIS; CANCER THERAPY; CARCINOGENESIS; CELL METABOLISM; CITRIC ACID CYCLE; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; TUMOR SUPPRESSOR GENE;

EID: 44449147036     PISSN: 15356108     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ccr.2008.05.005     Document Type: Review

References (81)

1. Al-Saffar N.M., Troy H., Ramirez de Molina A., Jackson L.E., Madhu B., Griffiths J.R., Leach M.O., Workman P., Lacal J.C., Judson I.R., and Chung Y.L. Noninvasive magnetic resonance spectroscopic pharmacodynamic markers of the choline kinase inhibitor MN58b in human carcinoma models. Cancer Res. 66 (2006) 427-434
2. Beckers A., Organe S., Timmermans L., Scheys K., Peeters A., Brusselmans K., Verhoeven G., and Swinnen J.V. Chemical inhibition of acetyl-CoA carboxylase induces growth arrest and cytotoxicity selectively in cancer cells. Cancer Res. 67 (2007) 8180-8187
3. Bensaad K., Tsuruta A., Selak M.A., Vidal M.N., Nakano K., Bartrons R., Gottlieb E., and Vousden K.H. TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell 126 (2006) 107-120
4. Bonnet S., Archer S.L., Allalunis-Turner J., Haromy A., Beaulieu C., Thompson R., Lee C.T., Lopaschuk G.D., Puttagunta L., Bonnet S., et al. A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth. Cancer Cell 11 (2007) 37-51
5. Brahimi-Horn M.C., Chiche J., and Pouyssegur J. Hypoxia signalling controls metabolic demand. Curr. Opin. Cell Biol. 19 (2007) 223-229
6. Brandon M., Baldi P., and Wallace D.C. Mitochondrial mutations in cancer. Oncogene 25 (2006) 4647-4662
7. Braunstein S., Karpisheva K., Pola C., Goldberg J., Hochman T., Yee H., Cangiarella J., Arju R., Formenti S.C., and Schneider R.J. A hypoxia-controlled cap-dependent to cap-independent translation switch in breast cancer. Mol. Cell 28 (2007) 501-512
8. Brizel D.M., and Esclamado R. Concurrent chemoradiotherapy for locally advanced, nonmetastatic, squamous carcinoma of the head and neck: consensus, controversy, and conundrum. J. Clin. Oncol. 24 (2006) 2612-2617
9. Chi S.L., Wahl M.L., Mowery Y.M., Shan S., Mukhopadhyay S., Hilderbrand S.C., Kenan D.J., Lipes B.D., Johnson C.E., Marusich M.F., et al. Angiostatin-like activity of a monoclonal antibody to the catalytic subunit of F1F0 ATP synthase. Cancer Res. 67 (2007) 4716-4724
10. Christofk H.R., Vander Heiden M.G., Harris M.H., Ramanathan A., Gerszten R.E., Wei R., Fleming M.D., Schreiber S.L., and Cantley L.C. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature 452 (2008) 230-233
11. Christofk H.R., Vander Heiden M.G., Wu N., Asara J.W., and Cantley L.C. Pyruvate kinase M2 is a phosphotyrosine binding protein. Nature 452 (2008) 181-186
12. Condeelis J., and Pollard J.W. Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell 124 (2006) 263-266
13. Counillon L., and Pouyssegur J. The expanding family of eucaryotic Na(+)/H(+) exchangers. J. Biol. Chem. 275 (2000) 1-4
14. Cramer T., Yamanishi Y., Clausen B.E., Forster I., Pawlinski R., Mackman N., Haase V.H., Jaenisch R., Corr M., Nizet V., et al. HIF-1alpha is essential for myeloid cell-mediated inflammation. Cell 112 (2003) 645-657
15. Culmsee C., and Mattson M.P. p53 in neuronal apoptosis. Biochem. Biophys. Res. Commun. 331 (2005) 761-777
16. Dang C.V., Kim J.-W., Gao P., and Yustein J. The interplay between MYC and HIF in cancer. Nat. Rev. Cancer 8 (2008) 51-56
17. Deberardinis R.J., Lum J.J., and Thompson C.B. Phosphatidylinositol 3-kinase-dependent modulation of carnitine palmitoyltransferase 1A expression regulates lipid metabolism during hematopoietic cell growth. J. Biol. Chem. 281 (2006) 37372-37380
18. Erler J.T., Bennewith K.L., Nicolau M., Dornhofer N., Kong C., Le Q.T., Chi J.T., Jeffrey S.S., and Giaccia A.J. Lysyl oxidase is essential for hypoxia-induced metastasis. Nature 440 (2006) 1222-1226
19. Esteban M.A., Tran M.G., Harten S.K., Hill P., Castellanos M.C., Chandra A., Raval R., O'Brien T.S., and Maxwell P.H. Regulation of E-cadherin expression by VHL and hypoxia-inducible factor. Cancer Res. 66 (2006) 3567-3575
20. Evans J.M., Ogston S.A., Emslie-Smith A., and Morris A.D. Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulfonylureas and metformin. Diabetologia 49 (2006) 930-936
21. Faivre S., Kroemer G., and Raymond E. Current development of mTOR inhibitors as anticancer agents. Nat. Rev. Drug Discov. 5 (2006) 671-688
22. Fantin V.R., St-Pierre J., and Leder P. Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer Cell 9 (2006) 425-434
23. Fischer K., Hoffmann P., Voelkl S., Meidenbauer N., Ammer J., Edinger M., Gottfried E., Schwarz S., Rothe G., Hoves S., et al. Inhibitory effect of tumor cell-derived lactic acid on human T cells. Blood 109 (2007) 3812-3819
24. Foldi M., Stickeler E., Bau L., Kretz O., Watermann D., Gitsch G., Kayser G., Zur Hausen A., and Coy J.F. Transketolase protein TKTL1 overexpression: A potential biomarker and therapeutic target in breast cancer. Oncol. Rep. 17 (2007) 841-845
25. Fukuda R., Zhang H., Kim J.W., Shimoda L., Dang C.V., and Semenza G.L. HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells. Cell 129 (2007) 111-122
26. Funes J.M., Quintero M., Henderson S., Martinez D., Qureshi U., Westwood C., Clements M.O., Bourboulia D., Pedley R.B., Moncada S., and Boshoff C. Transformation of human mesenchymal stem cells increases their dependency on oxidative phosphorylation for energy production. Proc. Natl. Acad. Sci. USA 104 (2007) 6223-6228
27. Galluzzi L., Larochette N., Zamzami N., and Kroemer G. Mitochondria as therapeutic targets for cancer chemotherapy. Oncogene 25 (2006) 4812-4830
28. Gao P., Zhang H., Dinavahi R., Li F., Xiang Y., Raman V., Bhujwalla Z.M., Felsher D.W., Cheng L., Pevsner J., et al. HIF-dependent antitumorigenic effect of antioxidants in vivo. Cancer Cell 12 (2007) 230-238
29. Gatenby R.A., and Gillies R.J. Why do cancers have high aerobic glycolysis?. Nat. Rev. Cancer 4 (2004) 891-899
30. Glunde K., and Bhujwalla Z.M. Choline kinase alpha in cancer prognosis and treatment. Lancet Oncol. 8 (2007) 855-857
31. Gottlieb E., and Tomlinson I.P. Mitochondrial tumour suppressors: a genetic and biochemical update. Nat. Rev. Cancer 5 (2005) 857-866
32. Graff J.R., Konicek B.W., Vincent T.M., Lynch R.L., Monteith D., Weir S.N., Schwier P., Capen A., Goode R.L., Dowless M.S., et al. Therapeutic suppression of translation initiation factor eIF4E expression reduces tumor growth without toxicity. J. Clin. Invest. 117 (2007) 2638-2648
33. Hanahan D., and Weinberg R.A. The hallmarks of cancer. Cell 100 (2000) 57-70
34. Harris A.L. Hypoxia--a key regulatory factor in tumour growth. Nat. Rev. Cancer 2 (2002) 38-47
35. Hatzivassiliou G., Zhao F., Bauer D.E., Andreadis C., Shaw A.N., Dhanak D., Hingorani S.R., Tuveson D.A., and Thompson C.B. ATP citrate lyase inhibition can suppress tumor cell growth. Cancer Cell 8 (2005) 311-321
36. Igney F.H., and Krammer P.H. Death and anti-death: tumour resistance to apoptosis. Nat. Rev. Cancer 2 (2002) 277-288
37. Ishikawa K., Takenaga K., Akimoto M., Koshikawa N., Yamaguchi A., Imanishi H., Nakada K., Honma Y., and Hayashi J.-I. ROS-generating mitochondrial DNA mutations can regulate tumor cell metastasis. Science 320 (2008) 661-664
38. Kim J.W., Tchernyshyov I., Semenza G.L., and Dang C.V. HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab. 3 (2006) 177-185
39. Kim J.W., Gao P., Liu Y.C., Semenza G.L., and Dang C.V. Hypoxia-inducible factor 1 and dysregulated c-Myc cooperatively induce vascular endothelial growth factor and metabolic switches hexokinase 2 and pyruvate dehydrogenase kinase 1. Mol. Cell. Biol. 27 (2007) 7381-7393
40. Kim W., Yoon J.H., Jeong J.M., Cheon G.J., Lee T.S., Yang J.I., Park S.C., and Lee H.S. Apoptosis-inducing antitumor efficacy of hexokinase II inhibitor in hepatocellular carcinoma. Mol. Cancer Ther. 6 (2007) 2554-2562
41. Ko Y.H., Smith B.L., Wang Y., Pomper M.G., Rini D.A., Torbenson M.S., Hullihen J., and Pedersen P.L. Advanced cancers: eradication in all cases using 3-bromopyruvate therapy to deplete ATP. Biochem. Biophys. Res. Commun. 324 (2004) 269-275
42. Kondoh H., Lleonart M.E., Gil J., Wang J., Degan P., Peters G., Martinez D., Carnero A., and Beach D. Glycolytic enzymes can modulate cellular life span. Cancer Res. 65 (2005) 177-185
43. Kong D., Park E.J., Stephen A.G., Calvani M., Cardellina J.H., Monks A., Fisher R.J., Shoemaker R.H., and Melillo G. Echinomycin, a small-molecule inhibitor of hypoxia-inducible factor-1 DNA-binding activity. Cancer Res. 65 (2005) 9047-9055
44. Koukourakis M.I., Giatromanolaki A., Harris A.L., and Sivridis E. Comparison of metabolic pathways between cancer cells and stromal cells in colorectal carcinomas: a metabolic survival role for tumor-associated stroma. Cancer Res. 66 (2006) 632-637
45. Kroemer G., Galluzzi L., and Brenner C. Mitochondrial membrane permeabilization in cell death. Physiol. Rev. 87 (2007) 99-163
46. Langbein S., Zerilli M., Zur Hausen A., Staiger W., Rensch-Boschert K., Lukan N., Popa J., Ternullo M.P., Steidler A., Weiss C., et al. Expression of transketolase TKTL1 predicts colon and urothelial cancer patient survival: Warburg effect reinterpreted. Br. J. Cancer 94 (2006) 578-585
47. Lardner A. The effects of extracellular pH on immune function. J. Leukoc. Biol. 69 (2001) 522-530
48. Lopez-Rios F., Sanchez-Arago M., Garcia-Garcia E., Ortega A.D., Berrendero J.R., Pozo-Rodriguez F., Lopez-Encuentra A., Ballestin C., and Cuezva J.M. Loss of the mitochondrial bioenergetic capacity underlies the glucose avidity of carcinomas. Cancer Res. 67 (2007) 9013-9017
49. MacKenzie E.D., Selak M.A., Tennant D.A., Payne L.J., Crosby S., Frederiksen C.M., Watson D.G., and Gottlieb E. Cell-permeating alpha-ketoglutarate derivatives alleviate pseudohypoxia in succinate dehydrogenase-deficient cells. Mol. Cell. Biol. 27 (2007) 3282-3289
50. Mankoff D.A., Eary J.F., Link J.M., Muzi M., Rajendran J.G., Spence A.M., and Krohn K.A. Tumor-specific positron emission tomography imaging in patients: [18F] fluorodeoxyglucose and beyond. Clin. Cancer Res. 13 (2007) 3460-3469
51. Manning B.D., and Cantley L.C. AKT/PKB signaling: navigating downstream. Cell 129 (2007) 1261-1274
52. Matoba S., Kang J.G., Patino W.D., Wragg A., Boehm M., Gavrilova O., Hurley P.J., Bunz F., and Hwang P.M. p53 regulates mitochondrial respiration. Science 312 (2006) 1650-1653
53. Mazurek S., Boschek C.B., Hugo F., and Eigenbrodt E. Pyruvate kinase type M2 and its role in tumor growth and spreading. Semin. Cancer Biol. 15 (2005) 300-308
54. Miyamoto S., Murphy A.N., and Brown J.H. Akt mediates mitochondrial protection in cardiomyocytes through phosphorylation of mitochondrial hexokinase-II. Cell Death Differ. 15 (2008) 521-529. 10.1038/sj.cdd.4402285 Published online December 7, 2007
55. Morgan P.E., Pastorekova S., Stuart-Tilley A.K., Alper S.L., and Casey J.R. Interactions of transmembrane carbonic anhydrase, CAIX, with bicarbonate transporters. Am. J. Physiol. Cell Physiol. 293 (2007) C738-C748
56. Munn D.H., and Mellor A.L. Indoleamine 2,3-dioxygenase and tumor-induced tolerance. J. Clin. Invest. 117 (2007) 1147-1154
57. Nawashiro H., Otani N., Shinomiya N., Fukui S., Ooigawa H., Shima K., Matsuo H., Kanai Y., and Endou H. L-type amino acid transporter 1 as a potential molecular target in human astrocytic tumors. Int. J. Cancer 119 (2006) 484-492
58. Papandreou I., Cairns R.A., Fontana L., Lim A.L., and Denko N.C. HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metab. 3 (2006) 187-197
59. Pastorino J.G., Hoek J.B., and Shulga N. Activation of glycogen synthase kinase 3beta disrupts the binding of hexokinase II to mitochondria by phosphorylating voltage-dependent anion channel and potentiates chemotherapy-induced cytotoxicity. Cancer Res. 65 (2005) 10545-10554
60. Pedersen P.L. Warburg, me and Hexokinase 2: Multiple discoveries of key molecular events underlying one of cancers' most common phenotypes, the "Warburg Effect", i.e., elevated glycolysis in the presence of oxygen. J. Bioenerg. Biomembr. 39 (2007) 211-222
61. Pennacchietti S., Michieli P., Galluzzo M., Mazzone M., Giordano S., and Comoglio P.M. Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene. Cancer Cell 3 (2003) 347-361
62. Pouyssegur J., Dayan F., and Mazure N.M. Hypoxia signalling in cancer and approaches to enforce tumour regression. Nature 441 (2006) 437-443
63. Puccetti P., and Grohmann U. IDO and regulatory T cells: a role for reverse signalling and non-canonical NF-kappaB activation. Nat. Rev. Immunol. 7 (2007) 817-823
64. Robey R.B., and Hay N. Mitochondrial hexokinases, novel mediators of the antiapoptotic effects of growth factors and Akt. Oncogene 25 (2006) 4683-4696
65. Semenza G.L. Hypoxia-inducible factor 1 (HIF-1) pathway. Sci. STKE 2007 (2007) cm8
66. Shaw R.J. Glucose metabolism and cancer. Curr. Opin. Cell Biol. 18 (2006) 598-608
67. Shaw R.J., and Cantley L.C. Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature 441 (2006) 424-430
68. Simons A.L., Ahmad I.M., Mattson D.M., Dornfeld K.J., and Spitz D.R. 2-Deoxy-D-glucose combined with cisplatin enhances cytotoxicity via metabolic oxidative stress in human head and neck cancer cells. Cancer Res. 67 (2007) 3364-3370
69. Stetak A., Veress R., Ovadi J., Csermely P., Keri G., and Ullrich A. Nuclear translocation of the tumor marker pyruvate kinase M2 induces programmed cell death. Cancer Res. 67 (2007) 1602-1608
70. Swietach P., Vaughan-Jones R.D., and Harris A.L. Regulation of tumor pH and the role of carbonic anhydrase 9. Cancer Metastasis Rev. 26 (2007) 299-310
71. Taylor C.T., and Pouyssegur J. Oxygen, hypoxia, and stress. Ann. N Y Acad. Sci. 1113 (2007) 87-94
72. Thiry A., Dogne J.M., Masereel B., and Supuran C.T. Targeting tumor-associated carbonic anhydrase IX in cancer therapy. Trends Pharmacol. Sci. 27 (2006) 566-573
73. Tomiyama A., Serizawa S., Tachibana K., Sakurada K., Samejima H., Kuchino Y., and Kitanaka C. Critical role for mitochondrial oxidative phosphorylation in the activation of tumor suppressors Bax and Bak. J. Natl. Cancer Inst. 98 (2006) 1462-1473
74. Wang H.Q., Altomare D.A., Skele K.L., Poulikakos P.I., Kuhajda F.P., Di Cristofano A., and Testa J.R. Positive feedback regulation between AKT activation and fatty acid synthase expression in ovarian carcinoma cells. Oncogene 24 (2005) 3574-3582
75. Warburg O., Posener K., and Negelein E. Über den Stoffwechsel der Tumoren. Biochem. Z. 152 (1924) 319-344
76. Yang M.H., Wu M.Z., Chiou S.H., Chen P.M., Chang S.Y., Liu C.J., Teng S.C., and Wu K.J. Direct regulation of TWIST by HIF-1alpha promotes metastasis. Nat. Cell Biol. 10 (2008) 295-305
77. Yoon S., Lee M.Y., Park S.W., Moon J.S., Koh Y.K., Ahn Y.H., Park B.W., and Kim K.S. Up-regulation of acetyl-CoA carboxylase alpha and fatty acid synthase by human epidermal growth factor receptor 2 at the translational level in breast cancer cells. J. Biol. Chem. 282 (2007) 26122-26131
78. Zhang H., Gao P., Fukuda R., Kumar G., Krishnamachary B., Zeller K.I., Dang C.V., and Semenza G.L. HIF-1 inhibits mitochondrial biogenesis and cellular respiration in VHL-deficient renal cell carcinoma by repression of C-MYC activity. Cancer Cell 11 (2007) 407-420
79. Zhou S., Kachhap S., Sun W., Wu G., Chuang A., Poeta L., Grumbine L., Mithani S.K., Chatterjee A., Koch W., et al. Frequency and phenotypic implications of mitochondrial DNA mutations in human squamous cell cancers of the head and neck. Proc. Natl. Acad. Sci. USA 104 (2007) 7540-7545
80. Zitvogel L., Tesniere A., and Kroemer G. Cancer despite immunosurveillance: immunoselection and immunosubversion. Nat. Rev. Immunol. 6 (2006) 715-727
81. Zoratti M., and Szabo I. The mitochondrial permeability transition. Biochim. Biophys. Acta 1241 (1995) 139-176