New aspects of the Warburg effect in cancer cell biology

Seminars in Cell and Developmental Biology

Volumn 23, Issue 4, 2012, Pages 352-361

  Bensinger, Steven J ^a   Christofk, Heather R ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Aerobic glycolysis; Cancer; Metabolism; Mitochondria; Warburg effect

Indexed keywords

ADENOSINE TRIPHOSPHATE; FLUORODEOXYGLUCOSE; MICRORNA;

CANCER CELL; CANCER RESISTANCE; CANCER STEM CELL; CYTOLOGY; GENOMICS; GLUCOSE METABOLISM; GLYCOLYSIS; HUMAN; MITOCHONDRION; MOLECULAR MECHANICS; POSITRON EMISSION TOMOGRAPHY; REVIEW; WARBURG EFFECT;

EID: 84861964103     PISSN: 10849521     EISSN: 10963634     Source Type: Journal    
DOI: 10.1016/j.semcdb.2012.02.003     Document Type: Review

References (117)

1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011;144:646-74.
2. Warburg O., Posener K., Negelein E. über den stoffwechsel der carcinomzelle. Biochem Z 1924, 152:309-344.
3. Minami S. Versuche an überlebendem carcinomgewebe. Biochem Z 1923, 142:334-350.
4. Koppenol WH, Bounds PL, Dang CV. Otto Warburg's contributions to current concepts of cancer metabolism. Nat Rev Cancer 2011;11:325-37.
5. Kelloff G.J., Hoffman J.M., Johnson B., Scher H.I., Siegel B.A., Cheng E.Y., et al. Progress and promise of FDG-PET imaging for cancer patient management and oncologic drug development. Clin Cancer Res 2005, 11:2785-2808.
6. Personal communication from Dr. Johannes Czernin, UCLA.
7. 18F] 2-deoxy-2-fluoro-d-glucose. J Nucl Med 1978, 19:1154-1161.
8. Cairns RA, Harris IS, Mak TW. Regulation of cancer cell metabolism. Nat Rev Cancer 2011;11:85-95.
9. Majumder P.K., Febbo P.G., Bikoff R., Berger R., Xue Q., McMahon L.M., 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. Shackelford D.B., Vasquez D.S., Corbeil J., Wu S., Leblanc M., Wu C.L., et al. mTOR and HIF-1alpha-mediated tumor metabolism in an LKB1 mouse model of Peutz-Jeghers syndrome. Proc Natl Acad Sci USA 2009, 106:11137-11142.
11. Palaskas N, Larson SM, Schultz N, Komisopoulou E, Wong J, Rohle D et al. 18F-fluorodeoxy-glucose positron emission tomography marks MYC-overexpressing human basal-like breast cancers. Cancer Res 2011;71:5164-74.
12. Semenza GL. HIF-1: upstream and downstream of cancer metabolism. Curr Opin Genet Dev 2010;20:51-6.
13. 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.
14. 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.
15. 2 availability on human cancer. Nat Rev Cancer 2008, 8:967-975.
16. Osthus R.C., Shim H., Kim S., Li Q., Reddy R., Mukherjee M., et al. Deregulation of glucose transporter 1 and glycolytic gene expression by c-Myc. J Biol Chem 2000, 275:21797-21800.
17. 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 USA 1997, 94:6658-6663.
18. Dang C.V., Kim J.W., Gao P., Yustein J. The interplay between MYC and HIF in cancer. Nat Rev Cancer 2008, 8:51-56.
19. 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, 458:762-765.
20. Dang CV. Rethinking the Warburg effect with Myc micromanaging glutamine metabolism. Cancer Res 2010;70:859-62.
21. 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.
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. Vousden K.H., Ryan K.M. p53 and metabolism. Nat Rev Cancer 2009, 9:691-700.
24. Villena J.A., Kralli A. ERRalpha: a metabolic function for the oldest orphan. Trends Endocrinol Metab 2008, 19:269-276.
25. Michalek R.D., Gerriets V.A., Nichols A.G., Inoue M., Kazmin D., Chang C.Y., et al. Estrogen-related receptor-alpha is a metabolic regulator of effector T-cell activation and differentiation. Proc Natl Acad Sci USA 2011, 108:18348-18353.
26. Tennessen J.M., Baker K.D., Lam G., Evans J., Thummel C.S. The Drosophila estrogen-related receptor directs a metabolic switch that supports developmental growth. Cell Metab 2011, 13:139-148.
27. Chang C.Y., Kazmin D., Jasper J.S., Kunder R., Zuercher W.J., McDonnell D.P. The metabolic regulator ERRalpha, a downstream target of HER2/IGF-1R, as a therapeutic target in breast cancer. Cancer Cell 2011, 20:500-510.
28. Jurica M.S., Mesecar A., Heath P.J., Shi W., Nowak T., Stoddard B.L. The allosteric regulation of pyruvate kinase by fructose-1,6-bisphosphate. Structure 1998, 6:195-210.
29. 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.
30. Luo W, Hu H, Chang R, Zhong J, Knabel M, O'Meally R, et al. Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1. Cell 2011;145:732-44.
31. Dombrauckas J.D., Santarsiero B.D., Mesecar A.D. Structural basis for tumor pyruvate kinase M2 allosteric regulation and catalysis. Biochemistry 2005, 44:9417-9429.
32. Christofk H.R., Vander Heiden M.G., Wu N., Asara J.M., Cantley L.C. Pyruvate kinase M2 is a phosphotyrosine-binding protein. Nature 2008, 452:181-186.
33. 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;480:118-22.
34. 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.
35. Okar D.A., Lange A.J. Fructose-2,6-bisphosphate and control of carbohydrate metabolism in eukaryotes. Biofactors 1999, 10:1-14.
36. 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 USA 1999, 96:3047-3052.
37. 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.
38. Mahlknecht U., Chesney J., Hoelzer D., Bucala R. Cloning and chromosomal characterization of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 gene (PFKFB3, iPFK2). Int J Oncol 2003, 23:883-891.
39. 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.
40. Minchenko O., Opentanova I., Caro J. Hypoxic regulation of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene family (PFKFB-1-4) expression in vivo. FEBS Lett 2003, 554:264-270.
41. Sakakibara R., Kato M., Okamura N., Nakagawa T., Komada Y., Tominaga N., et al. Characterization of a human placental fructose-6-phosphate, 2-kinase/fructose-2,6-bisphosphatase. J Biochem 1997, 122:122-128.
42. Telang S., Yalcin A., Clem A.L., Bucala R., Lane A.N., Eaton J.W., et al. Ras transformation requires metabolic control by 6-phosphofructo-2-kinase. Oncogene 2006, 25:7225-7234.
43. Reddy MM, Fernandes MS, Deshpande A, Weisberg E, Inguilizian HV, 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;26:481-9.
44. Marotta LL, Almendro V, Marusyk A, Shipitsin M, Schemme J, Walker SR, et al. The JAK2/STAT3 signaling pathway is required for growth of CD44CD24 stem cell-like breast cancer cells in human tumors. J Clin Invest 2011;121:2723-35.
45. Kennedy KM, Dewhirst MW. Tumor metabolism of lactate: the influence and therapeutic potential for MCT and CD147 regulation. Future Oncol 2010;6:127-48.
46. Pertega-Gomes N, Vizcaino JR, Miranda-Goncalves V, Pinheiro C, Silva J, Pereira H, et al. Monocarboxylate transporter 4 (MCT4) and CD147 overexpression is associated with poor prognosis in prostate cancer. BMC Cancer 2011;11:312.
47. Pinheiro C, Albergaria A, Paredes J, Sousa B, Dufloth R, Vieira D, et al. Monocarboxylate transporter 1 is up-regulated in basal-like breast carcinoma. Histopathology 2010;6:860-7.
48. 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.
49. Robey R.B., Hay N. Is Akt the Warburg kinase? - Akt-energy metabolism interactions and oncogenesis. Semin Cancer Biol 2009, 19:25-31.
50. Hitosugi T., Kang S., Vander Heiden M.G., Chung T.W., Elf S., Lythgoe K., et al. Tyrosine phosphorylation inhibits PKM2 to promote the Warburg effect and tumor growth. Sci Signal 2009, 2:ra73.
51. Lv L, Li D, Zhao D, Lin R, Chu Y, Zhang H, et al. Acetylation targets the M2 isoform of pyruvate kinase for degradation through chaperone-mediated autophagy and promotes tumor growth. Mol Cell 2011;42:719-30.
52. Anastasiou D, Poulogiannis G, Asara JM, Boxer MB, Jiang JK, Shen M, et al. Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to antioxidant responses. Science 2011;334:1278-83.
53. Mazurek S., Grimm H., Boschek C.B., Vaupel P., Eigenbrodt E. Pyruvate kinase type M2: a crossroad in the tumor metabolome. Br J Nutr 2002, 87(Suppl. 1):S23-S29.
54. 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.
55. Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., et al. Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nat Biotechnol 2005, 23:94-101.
56. Wu F, Wang P, Zhang J, Young LC, Lai R, Li L. Studies of phosphoproteomic changes induced by nucleophosmin-anaplastic lymphoma kinase (ALK) highlight deregulation of tumor necrosis factor (TNF)/Fas/TNF-related apoptosis-induced ligand signaling pathway in ALK-positive anaplastic large cell lymphoma. Mol Cell Proteomics 2010;9:1616-32.
57. Wang Q, Zhang Y, Yang C, Xiong H, Lin Y, Yao J, et al. Acetylation of metabolic enzymes coordinates carbon source utilization and metabolic flux. Science 2010;327:1004-7.
58. Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, et al. Regulation of cellular metabolism by protein lysine acetylation. Science 2010;327:1000-4.
59. Bartel D.P. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004, 116:281-297.
60. Calin G.A., Dumitru C.D., Shimizu M., Bichi R., Zupo S., Noch E., et al. Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA 2002, 99:15524-15529.
61. Iorio M.V., Ferracin M., Liu C.G., Veronese A., Spizzo R., Sabbioni S., et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res 2005, 65:7065-7070.
62. Ventura A., Jacks T. MicroRNAs and cancer: short RNAs go a long way. Cell 2009, 136:586-591.
63. Eichner LJ, Perry MC, Dufour CR, Bertos N, Park M, St-Pierre J, et al. miR-378(*) mediates metabolic shift in breast cancer cells via the PGC-1beta/ERRgamma transcriptional pathway. Cell Metab 2010;12:352-61.
64. Favaro E, Ramachandran A, McCormick R, Gee H, Blancher C, Crosby M, et al. MicroRNA-210 regulates mitochondrial free radical response to hypoxia and krebs cycle in cancer cells by targeting iron sulfur cluster protein ISCU. PLoS One 2010;5:e10345.
65. Locasale JW, Grassian AR, Melman T, Lyssiotis CA, Mattaini KR, Bass AJ, et al. Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis. Nat Genet 2011;43:869-74.
66. Possemato R, Marks KM, Shaul YD, Pacold ME, Kim D, Birsoy K, et al. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature 2011;476:346-50.
67. Mullarky E, Mattaini KR, Vander Heiden MG, Cantley LC, Locasale JW. PHGDH amplification and altered glucose metabolism in human melanoma. Pigment Cell Melanoma Res 2011;6:1112-5.
68. Fang M, Shen Z, Huang S, Zhao L, Chen S, Mak TW, et al. The ER UDPase ENTPD5 promotes protein N-glycosylation, the Warburg effect, and proliferation in the PTEN pathway. Cell 2010;143:711-24.
69. Vander Heiden MG, Locasale JW, Swanson KD, Sharfi H, Heffron GJ, Amador-Noguez D, et al. Evidence for an alternative glycolytic pathway in rapidly proliferating cells. Science 2010;329:1492-9.
70. Locasale JW, Cantley LC. Metabolic flux and the regulation of Mammalian cell growth. Cell Metab 2011;14:443-51.
71. Warburg O. On the origin of cancer cells. Science 1956, 123:309-314.
72. Weinhouse S. On respiratory impairment in cancer cells. Science 1956, 124:267-269.
73. 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.
74. Rossignol R., Gilkerson R., Aggeler R., Yamagata K., Remington S.J., Capaldi R.A. Energy substrate modulates mitochondrial structure and oxidative capacity in cancer cells. Cancer Res 2004, 64:985-993.
75. + channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth. Cancer Cell 2007, 11:37-51.
76. Weinhouse S. Oxidative metabolism of neoplastic tissues. Adv Cancer Res 1955, 3:269-325.
77. Frezza C., Gottlieb E. Mitochondria in cancer: not just innocent bystanders. Semin Cancer Biol 2009, 19:4-11.
78. Bouillaud F., Ricquier D., Thibault J., Weissenbach J. Molecular approach to thermogenesis in brown adipose tissue: cDNA cloning of the mitochondrial uncoupling protein. Proc Natl Acad Sci USA 1985, 82:445-448.
79. Jacobsson A., Stadler U., Glotzer M.A., Kozak L.P. Mitochondrial uncoupling protein from mouse brown fat. Molecular cloning, genetic mapping, and mRNA expression. J Biol Chem 1985, 260:16250-16254.
80. Baffy G. Uncoupling protein-2 and cancer. Mitochondrion 2010, 10:243-252.
81. Samudio I., Fiegl M., Andreeff M. Mitochondrial uncoupling and the Warburg effect: molecular basis for the reprogramming of cancer cell metabolism. Cancer Res 2009, 69:2163-2166.
82. Sayeed A., Meng Z., Luciani G., Chen L.C., Bennington J.L., Dairkee S.H. Negative regulation of UCP2 by TGFbeta signaling characterizes low and intermediate-grade primary breast cancer. Cell Death Dis 2010, 1:e53.
83. Derdak Z., Mark N.M., Beldi G., Robson S.C., Wands J.R., Baffy G. The mitochondrial uncoupling protein-2 promotes chemoresistance in cancer cells. Cancer Res 2008, 68:2813-2819.
84. Wang F., Fu X., Chen X., Zhao Y. Mitochondrial uncoupling inhibits p53 mitochondrial translocation in TPA-challenged skin epidermal JB6 cells. PLoS One 2010, 5:e13459.
85. Wallace D.C. Mitochondria and cancer. Warburg addressed. Cold Spring Harb Symp Quant Biol 2005, 70:363-374.
86. 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.
87. 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.
88. 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.
89. 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.
90. 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.
91. Fox C.J., Hammerman P.S., Thompson C.B. Fuel feeds function: energy metabolism and the T-cell response. Nat Rev Immunol 2005, 5:844-852.
92. Zoncu R., Efeyan A., Sabatini D.M. mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol 2011, 12:21-35.
93. van Stipdonk M.J., Hardenberg G., Bijker M.S., Lemmens E.E., Droin N.M., Green D.R., et al. Dynamic programming of CD8+ T lymphocyte responses. Nat Immunol 2003, 4:361-365.
94. Hatzivassiliou G., Zhao F., Bauer D.E., Andreadis C., Shaw A.N., Dhanak D., et al. ATP citrate lyase inhibition can suppress tumor cell growth. Cancer Cell 2005, 8:311-321.
95. 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.
96. 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.
97. Mardis E.R., Ding L., Dooling D.J., Larson D.E., McLellan M.D., Chen K., et al. Recurring mutations found by sequencing an acute myeloid leukemia genome. N Engl J Med 2009, 361:1058-1066.
98. Yan H., Parsons D.W., Jin G., McLendon R., Rasheed B.A., Yuan W., et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med 2009, 360:765-773.
99. Parsons D.W., Jones S., Zhang X., Lin J.C., Leary R.J., Angenendt P., et al. An integrated genomic analysis of human glioblastoma multiforme. Science 2008, 321:1807-1812.
100. Hanahan D., Weinberg R.A. Hallmarks of cancer: the next generation. Cell 2011, 144:646-674.
101. 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.
102. Martinez-Outschoorn U.E., Balliet R.M., Rivadeneira D.B., Chiavarina B., Pavlides S., Wang C., et al. Oxidative stress in cancer associated fibroblasts drives tumor-stroma co-evolution: A new paradigm for understanding tumor metabolism, the field effect and genomic instability in cancer cells. Cell Cycle 2010, 9:3256-3276.
103. 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.
104. 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.
105. Nieman K.M., Kenny H.A., Penicka C.V., Ladanyi A., Buell-Gutbrod R., Zillhardt M.R., et al. Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nat Med 2011, 17:1498-1503.
106. Nomura D.K., Long J.Z., Niessen S., Hoover H.S., Ng S.W., Cravatt B.F. Monoacylglycerol lipase regulates a fatty acid network that promotes cancer pathogenesis. Cell 2010, 140:49-61.
107. Vander Heiden M.G. Targeting cancer metabolism: a therapeutic window opens. Nat Rev Drug Discov 2011, 10:671-684.
108. Tennant D.A., Duran R.V., Gottlieb E. Targeting metabolic transformation for cancer therapy. Nat Rev Cancer 2010, 10:267-277.
109. Biswas G., Anandatheerthavarada H.K., Avadhani N.G. Mechanism of mitochondrial stress-induced resistance to apoptosis in mitochondrial DNA-depleted C2C12 myocytes. Cell Death Differ 2005, 12:266-278.
110. Park S.Y., Chang I., Kim J.Y., Kang S.W., Park S.H., Singh K., et al. Resistance of mitochondrial DNA-depleted cells against cell death: role of mitochondrial superoxide dismutase. J Biol Chem 2004, 279:7512-7520.
111. Yang Z., Schumaker L.M., Egorin M.J., Zuhowski E.G., Guo Z., Cullen K.J. Cisplatin preferentially binds mitochondrial DNA and voltage-dependent anion channel protein in the mitochondrial membrane of head and neck squamous cell carcinoma: possible role in apoptosis. Clin Cancer Res 2006, 12:5817-5825.
112. Amuthan G., Biswas G., Ananadatheerthavarada H.K., Vijayasarathy C., Shephard H.M., Avadhani N.G. Mitochondrial stress-induced calcium signaling, phenotypic changes and invasive behavior in human lung carcinoma A549 cells. Oncogene 2002, 21:7839-7849.
113. Oliva C.R., Moellering D.R., Gillespie G.Y., Griguer C.E. Acquisition of chemoresistance in gliomas is associated with increased mitochondrial coupling and decreased ROS production. PLoS One 2011, 6:e24665.
114. Oliva C.R., Nozell S.E., Diers A., McClugage S.G., Sarkaria J.N., Markert J.M., et al. Acquisition of temozolomide chemoresistance in gliomas leads to remodeling of mitochondrial electron transport chain. J Biol Chem 2010, 285:39759-39767.
115. Vlashi E., Lagadec C., Vergnes L., Matsutani T., Masui K., Poulou M., et al. Metabolic state of glioma stem cells and nontumorigenic cells. Proc Natl Acad Sci USA 2011, 108:16062-16067.
116. Bao S., Wu Q., McLendon R.E., Hao Y., Shi Q., Hjelmeland A.B., et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 2006, 444:756-760.
117. Oermanna E.K., Wu J., Guan K.-L., Xiong Y. Alterations of metabolic genes and metabolites in cancer. Sem. Cell. Dev. Biol. 2012, 23:370-380.