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Metabolic pathways promoting cancer cell survival and growth

Abstract

Activation of oncogenes and loss of tumour suppressors promote metabolic reprogramming in cancer, resulting in enhanced nutrient uptake to supply energetic and biosynthetic pathways. However, nutrient limitations within solid tumours may require that malignant cells exhibit metabolic flexibility to sustain growth and survival. Here, we highlight these adaptive mechanisms and also discuss emerging approaches to probe tumour metabolism in vivo and their potential to expand the metabolic repertoire of malignant cells even further.

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Figure 1: Oncogenic signalling and nutrient availability influence cell metabolism.
Figure 2: Catabolic pathways support metabolism during nutrient stress.
Figure 3: Complex, compartmentalized pathways of NADPH production.
Figure 4: A model for metabolic heterogeneity in solid tumours.

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References

  1. Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 144, 646–674 (2011).

    Article  CAS  Google Scholar 

  2. Ying, H. et al. Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism. Cell 149, 656–670 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Flier, J. S., Mueckler, M. M., Usher, P. & Lodish, H. F. Elevated levels of glucose transport and transporter messenger RNA are induced by ras or src oncogenes. Science 235, 1492–1495 (1987).

    Article  CAS  PubMed  Google Scholar 

  4. Gaglio, D. et al. Oncogenic K-Ras decouples glucose and glutamine metabolism to support cancer cell growth. Mol. Syst. Biol. 7, 523 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Weinberg, F. et al. Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity. Proc. Natl Acad. Sci. USA 107, 8788–8793 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Son, J. et al. Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway. Nature 496, 101–105 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Shim, H. et al. c-Myc transactivation of LDH-A: implications for tumor metabolism and growth. Proc. Natl Acad. Sci. USA 94, 6658–6663 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Li, F. et al. Myc stimulates nuclearly encoded mitochondrial genes and mitochondrial biogenesis. Mol. Cell. Biol. 25, 6225–6234 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Wise, D. R. et al. Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Proc. Natl Acad. Sci. USA 105, 18782–18787 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Gao, P. et al. c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature 458, 762–765 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. DeBerardinis, R. J. & Cheng, T. Q's next: the diverse functions of glutamine in metabolism, cell biology and cancer. Oncogene 29, 313–324 (2010).

    Article  CAS  PubMed  Google Scholar 

  12. Yun, J. et al. Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells. Science 325, 1555–1559 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Le, A. et al. Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B cells. Cell Metab. 15, 110–121 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Yang, C. et al. Glioblastoma cells require glutamate dehydrogenase to survive impairments of glucose metabolism or Akt signaling. Cancer Res. 69, 7986–7993 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Cheng, T. et al. Pyruvate carboxylase is required for glutamine-independent growth of tumor cells. Proc. Natl Acad. Sci. USA 108, 8674–8679 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Birsoy, K. et al. Metabolic determinants of cancer cell sensitivity to glucose limitation and biguanides. Nature 508, 108–112 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Caro, P. et al. Metabolic signatures uncover distinct targets in molecular subsets of diffuse large B cell lymphoma. Cancer Cell 22, 547–560 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Vacanti, N. M. et al. Regulation of substrate utilization by the mitochondrial pyruvate carrier. Mol. Cell 56, 425–435 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Yang, C. et al. Glutamine oxidation maintains the TCA cycle and cell survival during impaired mitochondrial pyruvate transport. Mol. Cell 56, 414–424 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Zhang, J. et al. Asparagine plays a critical role in regulating cellular adaptation to glutamine depletion. Mol. Cell 56, 205–218 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. DeBerardinis, R. J. et al. Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc. Natl Acad. Sci. USA 104, 19345–19350 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Avramis, V. I. Asparaginases: biochemical pharmacology and modes of drug resistance. Anticancer Res. 32, 2423–2437 (2012).

    CAS  PubMed  Google Scholar 

  23. Kawedia, J. D. & Rytting, M. E. Asparaginase in acute lymphoblastic leukemia. Clin. Lymphoma Myeloma Leuk. 14, S14–S17 (2014).

    Article  PubMed  Google Scholar 

  24. Commisso, C. et al. Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells. Nature 497, 633–637 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Goldsmith, J., Levine, B. & Debnath, J. Autophagy and cancer metabolism. Methods Enzymol. 542, 25–57 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Marino, G., Niso-Santano, M., Baehrecke, E. H. & Kroemer, G. Self-consumption: the interplay of autophagy and apoptosis. Nat. Rev. Mol. Cell Biol. 15, 81–94 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Rabinowitz, J. D. & White, E. Autophagy and metabolism. Science 330, 1344–1348 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Lum, J. J. et al. Growth factor regulation of autophagy and cell survival in the absence of apoptosis. Cell 120, 237–248 (2005).

    Article  CAS  PubMed  Google Scholar 

  29. Deberardinis, R. J., Lum, J. J. & Thompson, C. B. Phosphatidylinositol 3-kinase-dependent modulation of carnitine palmitoyltransferase 1A expression regulates lipid metabolism during hematopoietic cell growth. J. Biol. Chem. 281, 37372–37380 (2006).

    Article  CAS  PubMed  Google Scholar 

  30. Lum, J. J., DeBerardinis, R. J. & Thompson, C. B. Autophagy in metazoans: cell survival in the land of plenty. Nat. Rev. Mol. Cell Biol. 6, 439–448 (2005).

    Article  CAS  PubMed  Google Scholar 

  31. Yang, S. et al. Pancreatic cancers require autophagy for tumor growth. Genes Dev. 25, 717–729 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Guo, J. Y. et al. Autophagy suppresses progression of K-ras-induced lung tumors to oncocytomas and maintains lipid homeostasis. Genes Dev. 27, 1447–1461 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Guo, J. Y. et al. Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis. Genes Dev. 25, 460–470 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Strohecker, A. M. et al. Autophagy sustains mitochondrial glutamine metabolism and growth of BrafV600E-driven lung tumors. Cancer Discov. 3, 1272–1285 (2013).

    Article  CAS  PubMed  Google Scholar 

  35. Karsli-Uzunbas, G. et al. Autophagy is required for glucose homeostasis and lung tumor maintenance. Cancer Discov. 4, 914–927 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Wang, T. J. et al. Metabolite profiles and the risk of developing diabetes. Nat. Med. 17, 448–453 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Walford, G. A. et al. Branched chain and aromatic amino acids change acutely following two medical therapies for type 2 diabetes mellitus. Metabolism 62, 1772–1778 (2013).

    Article  CAS  PubMed  Google Scholar 

  38. Newgard, C. B. et al. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab. 9, 311–326 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Mayers, J. R. et al. Elevation of circulating branched-chain amino acids is an early event in human pancreatic adenocarcinoma development. Nat. Med. 20, 1193–1198 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Tonjes, M. et al. BCAT1 promotes cell proliferation through amino acid catabolism in gliomas carrying wild-type IDH1. Nat. Med. 19, 901–908 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Swinnen, J. V., Brusselmans, K. & Verhoeven, G. Increased lipogenesis in cancer cells: new players, novel targets. Curr. Opin. Clin. Nutr. Metab. Care 9, 358–365 (2006).

    Article  CAS  PubMed  Google Scholar 

  42. Currie, E., Schulze, A., Zechner, R., Walther, T. C. & Farese, R. V. Jr Cellular fatty acid metabolism and cancer. Cell Metab. 18, 153–161 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. DeBerardinis, R. J., Lum, J. J., Hatzivassiliou, G. & Thompson, C. B. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab. 7, 11–20 (2008).

    Article  CAS  PubMed  Google Scholar 

  44. Bauer, D. E., Hatzivassiliou, G., Zhao, F., Andreadis, C. & Thompson, C. B. ATP citrate lyase is an important component of cell growth and transformation. Oncogene 24, 6314–6322 (2005).

    Article  CAS  PubMed  Google Scholar 

  45. Kamphorst, J. J. et al. Hypoxic and Ras-transformed cells support growth by scavenging unsaturated fatty acids from lysophospholipids. Proc. Natl Acad. Sci. USA 110, 8882–8887 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Young, R. M. et al. Dysregulated mTORC1 renders cells critically dependent on desaturated lipids for survival under tumor-like stress. Genes Dev. 27, 1115–1131 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Viale, A. et al. Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function. Nature 514, 628–632 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Nieman, K. M. et al. Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nat. Med. 17, 1498–1503 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Ackerman, D. & Simon, M. C. Hypoxia, lipids, and cancer: surviving the harsh tumor microenvironment. Trends Cell Biol. 24, 472–478 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Perez-Chacon, G., Astudillo, A. M., Balgoma, D., Balboa, M. A. & Balsinde, J. Control of free arachidonic acid levels by phospholipases A2 and lysophospholipid acyltransferases. Biochim. Biophys. Acta 1791, 1103–1113 (2009).

    Article  CAS  PubMed  Google Scholar 

  51. Psychogios, N. et al. The human serum metabolome. PLoS ONE 6, e16957 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Mashimo, T. et al. Acetate is a bioenergetic substrate for human glioblastoma and brain metastases. Cell 159, 1603–1614 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Comerford, S. A. et al. Acetate dependence of tumors. Cell 159, 1591–1602 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Schug, Z. T. et al. Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress. Cancer cell 27, 57–71 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Gorrini, C., Harris, I. S. & Mak, T. W. Modulation of oxidative stress as an anticancer strategy. Nat. Rev. Drug Discov. 12, 931–947 (2013).

    Article  CAS  PubMed  Google Scholar 

  56. Schieber, M. & Chandel, N. S. ROS function in redox signaling and oxidative stress. Curr. Biol. 24, R453–R462 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Shackelford, D. B. & Shaw, R. J. The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nat. Rev. Cancer 9, 563–575 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Faubert, B. et al. Loss of the tumor suppressor LKB1 promotes metabolic reprogramming of cancer cells via HIF-1alpha. Proc. Natl Acad. Sci. USA 111, 2554–2559 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Faubert, B. et al. AMPK is a negative regulator of the Warburg effect and suppresses tumor growth in vivo. Cell Metab. 17, 113–124 (2013).

    Article  CAS  PubMed  Google Scholar 

  60. Jeon, S. M., Chandel, N. S. & Hay, N. AMPK regulates NADPH homeostasis to promote tumour cell survival during energy stress. Nature 485, 661–665 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Lewis, C. A. et al. Tracing compartmentalized NADPH metabolism in the cytosol and mitochondria of Mammalian cells. Mol. Cell 55, 253–263 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Christensen, K. E. & MacKenzie, R. E. Mitochondrial one-carbon metabolism is adapted to the specific needs of yeast, plants and mammals. BioEssays 28, 595–605 (2006).

    Article  CAS  PubMed  Google Scholar 

  63. Fan, J. et al. Quantitative flux analysis reveals folate-dependent NADPH production. Nature 510, 298–302 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Ye, J. et al. Serine catabolism regulates mitochondrial redox control during hypoxia. Cancer Discov. 4, 1406–1417 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Lee, G. Y. et al. Comparative oncogenomics identifies PSMB4 and SHMT2 as potential cancer driver genes. Cancer Res 74, 3114–3126 (2014).

    Article  CAS  PubMed  Google Scholar 

  66. Jain, M. et al. Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation. Science 336, 1040–1044 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Labuschagne, C. F., van den Broek, N. J., Mackay, G. M., Vousden, K. H. & Maddocks, O. D. Serine, but not glycine, supports one-carbon metabolism and proliferation of cancer cells. Cell Rep. 7, 1248–1258 (2014).

    Article  CAS  PubMed  Google Scholar 

  68. Possemato, R. et al. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature 476, 346–350 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Locasale, J. W. et al. Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis. Nat. Genet. 43, 869–874 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Chaneton, B. et al. Serine is a natural ligand and allosteric activator of pyruvate kinase M2. Nature 491, 458–462 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Dang, L. et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462, 739–744 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Ward, P. S. 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 17, 225–234 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Li, B. et al. Fructose-1, 6-bisphosphatase opposes renal carcinoma progression. Nature 513, 251–255 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Andronesi, O. C. et al. Detection of 2-hydroxyglutarate in IDH-mutated glioma patients by in vivo spectral-editing and 2D correlation magnetic resonance spectroscopy. Sci. Transl. Med. 4, 116ra4 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Choi, C. et al. 2-hydroxyglutarate detection by magnetic resonance spectroscopy in IDH-mutated patients with gliomas. Nat. Med. 18, 624–629 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Elkhaled, A. et al. Magnetic resonance of 2-hydroxyglutarate in IDH1-mutated low-grade gliomas. Sci. Transl. Med. 4, 116ra115 (2012).

    Article  CAS  Google Scholar 

  77. Pope, W. B. et al. Non-invasive detection of 2-hydroxyglutarate and other metabolites in IDH1 mutant glioma patients using magnetic resonance spectroscopy. J. Neuro-oncol. 107, 197–205 (2012).

    Article  CAS  Google Scholar 

  78. Gallamini, A., Zwarthoed, C. & Borra, A. Positron Emission tomography (PET) in oncology. Cancers 6, 1821–1889 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  79. Mankoff, D. A. et al. Tumor-specific positron emission tomography imaging in patients: [18F] fluorodeoxyglucose and beyond. Clin. Cancer Res. 13, 3460–3469 (2007).

    Article  CAS  PubMed  Google Scholar 

  80. Wu, Z. et al. [(18)F](2S, 4S)-4-(3-Fluoropropyl)glutamine as a tumor imaging agent. Mol. Pharm. 11, 3852–3866 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Wachter, S. et al. 11C-acetate positron emission tomography imaging and image fusion with computed tomography and magnetic resonance imaging in patients with recurrent prostate cancer. J. Clin. Oncol. 24, 2513–2519 (2006).

    Article  PubMed  Google Scholar 

  82. Ploessl, K., Wang, L., Lieberman, B. P., Qu, W. & Kung, H. F. Comparative evaluation of 18F-labeled glutamic acid and glutamine as tumor metabolic imaging agents. J. Nucl. Med. 53, 1616–1624 (2012).

    Article  CAS  PubMed  Google Scholar 

  83. Oyama, N. et al. 11C-acetate PET imaging of prostate cancer: detection of recurrent disease at PSA relapse. J. Nucl. Med. 44, 549–555 (2003).

    CAS  PubMed  Google Scholar 

  84. Mena, E. et al. 11C-Acetate PET/CT in localized prostate cancer: a study with MRI and histopathologic correlation. J. Nucl. Med. 53, 538–545 (2012).

    Article  CAS  PubMed  Google Scholar 

  85. Qu, W. et al. Synthesis of optically pure 4-fluoro-glutamines as potential metabolic imaging agents for tumors. J. Am. Chem. Soc. 133, 1122–1133 (2011).

    Article  CAS  PubMed  Google Scholar 

  86. Venetti, S. et al. Glutamine-based PET imaging facilitates enhanced metabolic evaluation of gliomas in vivo. Sci. Trans. Med. 7, 274ra17 (2015).

    Google Scholar 

  87. Fan, T. W. et al. Altered regulation of metabolic pathways in human lung cancer discerned by 13C stable isotope-resolved metabolomics (SIRM). Mol. Cancer 8, 41 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Maher, E. A. et al. Metabolism of [U-13C]glucose in human brain tumors in vivo. NMR Biomed. 25, 1234–1244 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Marin-Valencia, I. et al. Glucose metabolism via the pentose phosphate pathway, glycolysis and Krebs cycle in an orthotopic mouse model of human brain tumors. NMR Biomed. 25, 1177–1186 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Marin-Valencia, I. et al. Analysis of tumor metabolism reveals mitochondrial glucose oxidation in genetically diverse human glioblastomas in the mouse brain in vivo. Cell Metab. 15, 827–837 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Sellers, K. et al. Pyruvate carboxylase is critical in non-small cell lung cancer. J. Clin. Invest. 125, 687–698 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  92. Clarke, D. D. & Sokoloff, L. in Basic Neurochemistry: Molecular, Cellular and Medical Aspects 6th edn (eds Siegel, G. J., Agranoff, B. W., Albers, R. W., Fisher, S. K. & Uhler, M. D.) Ch. 31 (Lippincott-Raven, 1999).

    Google Scholar 

  93. Yang, Z. J., Chee, C. E., Huang, S. & Sinicrope, F. A. The role of autophagy in cancer: therapeutic implications. Mol. Cancer Ther. 10, 1533–1541 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Farrow, J. M., Yang, J. C. & Evans, C. P. Autophagy as a modulator and target in prostate cancer. Nat. Rev. Urol. 11, 508–516 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Amaravadi, R. K. et al. Principles and current strategies for targeting autophagy for cancer treatment. Clin. Cancer Res. 17, 654–666 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Wilson, P. M., Danenberg, P. V., Johnston, P. G., Lenz, H. J. & Ladner, R. D. Standing the test of time: targeting thymidylate biosynthesis in cancer therapy. Nat. Rev. Clin. Oncol. 11, 282–298 (2014).

    Article  CAS  PubMed  Google Scholar 

  97. Glasauer, A. & Chandel, N. S. Targeting antioxidants for cancer therapy. Biochem. Pharmacol. 92, 90–101 (2014).

    Article  CAS  PubMed  Google Scholar 

  98. Yuneva, M. O. et al. The metabolic profile of tumors depends on both the responsible genetic lesion and tissue type. Cell Metabol. 15, 157–170 (2012).

    Article  CAS  Google Scholar 

  99. Yabu, M. et al. IL-23-dependent and -independent enhancement pathways of IL-17A production by lactic acid. Int. Immunol. 23, 29–41 (2011).

    Article  CAS  PubMed  Google Scholar 

  100. Lisanti, M. P. et al. Understanding the “lethal” drivers of tumor-stroma co-evolution: emerging role(s) for hypoxia, oxidative stress and autophagy/mitophagy in the tumor micro-environment. Cancer Biol. Ther. 10, 537–542 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Martinez-Outschoorn, U. E. 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 9, 3256–3276 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Yachida, S. et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature 467, 1114–1117 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Vogelstein, B. et al. Cancer genome landscapes. Science 339, 1546–1558 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Ding, L. et al. Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature 481, 506–510 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank members of the DeBerardinis lab for their helpful comments on this review. R.J.D. is supported by grants from the N.I.H. (CA157996), Cancer Prevention and Research Institute of Texas (RP130272) and V Foundation. L.K.B. is supported by an N.I.H. Training Grant (5T32CA124334-08).

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L.K.B. and R.J.D. wrote the paper and designed the illustrations.

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Correspondence to Ralph J. DeBerardinis.

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Boroughs, L., DeBerardinis, R. Metabolic pathways promoting cancer cell survival and growth. Nat Cell Biol 17, 351–359 (2015). https://doi.org/10.1038/ncb3124

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