Drivers of the warburg phenotype

Cancer Journal (United States)

Volumn 21, Issue 2, 2015, Pages 56-61

  Cairns, Rob A ^a  

^a PRINCESS MARGARET HOSPITAL   (Canada)

Author keywords

biosynthesis; glycolysis; hypoxia; microenvironment; oncogene; respiration; tumor suppressor; Warburg effect

Indexed keywords

ADENOSINE TRIPHOSPHATE; GLUCOSE; GLUCOSE TRANSPORTER 1; HEXOKINASE; HYPOXIA INDUCIBLE FACTOR; LACTIC ACID; MONOCARBOXYLATE TRANSPORTER; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN P53; PYRUVATE KINASE;

CELL PROLIFERATION; CELL SURVIVAL; CITRIC ACID CYCLE; GLUCOSE METABOLISM; GLYCOLYSIS; HUMAN; MALIGNANT NEOPLASTIC DISEASE; METABOLIC DISORDER; MOLECULAR PATHOLOGY; NONHUMAN; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; TUMOR CELL; TUMOR MICROENVIRONMENT; WARBURG EFFECT; ANIMAL; CELL TRANSFORMATION; GENETICS; METABOLISM; MITOCHONDRION; NEOPLASM; OXIDATIVE PHOSPHORYLATION; PHENOTYPE; TRANSPORT AT THE CELLULAR LEVEL;

ANIMALS; BIOLOGICAL TRANSPORT; CELL TRANSFORMATION, NEOPLASTIC; GLUCOSE; GLYCOLYSIS; HUMANS; MITOCHONDRIA; NEOPLASMS; OXIDATIVE PHOSPHORYLATION; PHENOTYPE; SIGNAL TRANSDUCTION;

EID: 84926662205     PISSN: 15289117     EISSN: 1540336X     Source Type: Journal    
DOI: 10.1097/PPO.0000000000000106     Document Type: Review

References (49)

1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646-674.
2. Warburg O. On the origin of cancer cells. Science. 1956;123:309-314.
3. Warburg O. On respiratory impairment in cancer cells. Science. 1956;124: 269-270.
4. Weinhouse S. TheWarburg hypothesis fifty years later. Z Krebsforsch Klin Onkol. 1976;87:115-126.
5. Fogal V, Richardson AD, Karmali PP, et al. Mitochondrial p32 protein is a critical regulator of tumor metabolism via maintenance of oxidative phosphorylation. Mol Cell Biol. 2010;30:1303-1318.
6. Weinberg F, Hamanaka R, Wheaton WW, et al. Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity. Proc Natl Acad Sci U S A. 2010;107:8788-8793.
7. Seyfried TN, Flores RE, Poff AM, et al. Cancer as a metabolic disease: implications for novel therapeutics. Carcinogenesis. 2014;35:515-527.
8. Rohren EM, Turkington TG, Coleman RE. Clinical applications of PET in oncology. Radiology. 2004;231:305-332.
9. Gambhir SS. Molecular imaging of cancer with positron emission tomography. Nat Rev Cancer. 2002;2:683-693.
10. Cairns RA, Harris IS, Mak TW. Regulation of cancer cell metabolism. Nat Rev Cancer. 2011;11:85-95.
11. vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324:1029-1033.
12. Gillies RJ, Gatenby RA. Adaptive landscapes and emergent phenotypes: why do cancers have high glycolysis? J Bioenerg Biomembr. 2007;39:251-257.
13. Epstein T, Xu L, Gillies RJ, et al. Separation of metabolic supply and demand: aerobic glycolysis as a normal physiological response to fluctuating energetic demands in the membrane. Cancer Metab. 2014;2:7.
14. Fang M, Shen Z, Huang S, et al. The ER UDPase ENTPD5 promotes protein N-glycosylation, the Warburg effect, and proliferation in the PTEN pathway. Cell. 2010;143:711-724.
15. Israelsen WJ, vander Heiden MG. ATP consumption promotes cancer metabolism. Cell. 2010;143:669-671.
16. Wang T,Marquardt C, Foker J. Aerobic glycolysis during lymphocyte proliferation. Nature. 1976;261:702-705.
17. Michalek RD, Rathmell JC. The metabolic life and times of a T-cell. Immunol Rev. 2010;236:190-202.
18. Lochner M, Berod L, Sparwasser T. Fatty acid metabolism in the regulation of T cell function. Trends Immunol. 2015;36:81-91.
19. Turner J, Quek L-E, TitmarshD, et al. Metabolic profiling and flux analysis of MEL-2 human embryonic stemcells during exponential growth at physiological and atmospheric oxygen concentrations. PLoS One. 2014;9:e112757.
20. Chen Z, Odstrcil EA, Tu BP, et al. Restriction of DNA replication to the reductive phase of the metabolic cycle protects genome integrity. Science. 2007;316:1916-1919.
21. Agathocleous M, Love NK, Randlett O, et al. Metabolic differentiation in the embryonic retina. Nat Cell Biol. 2012;14:859-864.
22. Suda T, Takubo K, Semenza GL. Metabolic regulation of hematopoietic stem cells in the hypoxic niche. Cell Stem Cell. 2011;9:298-310.
23. Takubo K, Nagamatsu G, Kobayashi CI, et al. Regulation of glycolysis by Pdk functions as a metabolic checkpoint for cell cycle quiescence in hematopoietic stem cells. Cell Stem Cell. 2013;12:49-61.
24. Parmar K, Mauch P, Vergilio J-A, et al. Distribution of hematopoietic stem cells in the bone marrow according to regional hypoxia. Proc Natl Acad Sci U S A. 2007;104:5431-5436.
25. Liu X, Zheng H, YuW-M, et al. Maintenance ofmouse hematopoietic stem cells ex vivo by reprogramming cellular metabolism. Blood. 2015;125: 1562-1565.
26. Oburoglu L, Tardito S, Fritz V, et al. Glucose and glutamine metabolism regulate human hematopoietic stem cell lineage specification. Cell Stem Cell. 2014;15(2):169-184.
27. Semenza GL. HIF-1: upstream and downstream of cancer metabolism. Curr Opin Genet Dev. 2010;20:51-56.
28. Papandreou I, Cairns RA, Fontana L, et al. HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metab. 2006;3:187-197.
29. Denko NC. Hypoxic regulation of metabolism offers new opportunities for anticancer therapy. Expert Rev Anticancer Ther. 2014;14:979-981.
30. Robey RB, Hay N. Is Akt the "Warburg kinase"?-Akt-energy metabolism interactions and oncogenesis. Semin Cancer Biol. 2009;19:25-31.
31. Lee P, Vousden KH, Cheung EC. TIGAR, TIGAR, burning bright. Cancer Metab. 2014;2:1.
32. Matoba S, Kang J-G, Patino WD, et al. p53 regulates mitochondrial respiration. Science. 2006;312:1650-1653.
33. Wolf A, Agnihotri S, Micallef J, et al. Hexokinase 2 is a key mediator of aerobic glycolysis and promotes tumor growth in human glioblastoma multiforme. J Exp Med. 2011;208:313-326.
34. Wang L, Xiong H, Wu F, et al. Hexokinase 2-mediated Warburg effect is required for PTEN-and p53-deficiency-driven prostate cancer growth. Cell Rep. 2014;8:1461-1474.
35. Patra KC, Wang Q, Bhaskar PT, et al. Hexokinase 2 is required for tumor initiation and maintenance and its systemic deletion is therapeutic in mouse models of cancer. Cancer Cell. 2013;24:213-228.
36. Christofk HR, vander HeidenMG, HarrisMH, et al. TheM2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature. 2008;452:230-233.
37. vander HeidenMG, Locasale JW, Swanson KD, et al. Evidence for an alternative glycolytic pathway in rapidly proliferating cells. Science. 2010;329: 1492-1499.
38. Bluemlein K, Grüning N-M, Feichtinger RG, et al. No evidence for a shift in pyruvate kinase PKM1 to PKM2 expression during tumorigenesis. Oncotarget. 2011;2:393-400.
39. Luo W, Hu H, Chang R, et al. Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1. Cell. 2011;145:732-744.
40. Iqbal MA, Gupta V, Gopinath P, et al. Pyruvate kinase M2 and cancer: an updated assessment. FEBS Lett. 2014;588:2685-2692.
41. Kim J-W, Tchernyshyov I, Semenza GL, et al. HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab. 2006;3:177-185.
42. Ganapathy V, Thangaraju M, Prasad PD. Nutrient transporters in cancer: relevance to Warburg hypothesis and beyond. Pharmacol Ther. 2009; 121:29-40.
43. Weihua Z, Tsan R, HuangW-C, et al. Survival of cancer cells is maintained by EGFR independent of its kinase activity. Cancer Cell. 2008;13: 385-393.
44. Herzig S, Raemy E, Montessuit S, et al. Identification and functional expression of the mitochondrial pyruvate carrier. Science. 2012;337:93-96.
45. Bricker DK, Taylor EB, Schell JC, et al. A mitochondrial pyruvate carrier required for pyruvate uptake in yeast, Drosophila, and humans. Science. 2012;337:96-100.
46. Halestrap AP. The mitochondrial pyruvate carrier: has it been unearthed at last? Cell Metab. 2012;16:141-143.
47. Schell JC, Olson KA, Jiang L, et al. A role for the mitochondrial pyruvate carrier as a repressor of the Warburg effect and colon cancer cell growth. Mol Cell. 2014;56:400-413.
48. Sonveaux P, Végran F, Schroeder T, et al. Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice. J Clin Invest. 2008;118: 3930-3942.
49. Ewald JC, Reich S, Baumann S, et al. Engineering genetically encoded nanosensors for real-time in vivo measurements of citrate concentrations. PLoS One. 2011;6:e28245.