Advertisement

Tumorigenesis and Metabolism Disorder

Chapter
  • 280 Downloads

Abstract

During the tumorigenic process, cancer cells always readjust their metabolism to obtain the energy and metabolites to sustain their increased proliferation. The activation of oncogenes and the loss of tumor suppressors are key molecular events controlling the acquisition of metabolic reprogramming. Many factors can cause the occurrence of metabolic reprogramming in tumor cells, such as changes of tumor microenvironment, activation of oncogenes, and inactivation of tumor suppressor genes. Metabolic pathways such as glycolysis and glutamine metabolism can be altered in tumor cells, thereby making these metabolic pathways adapted to tumor survival and proliferation. These metabolic pathways of tumor cells generate specific metabolites, which have been reported as new clues for cancer treatment. Therefore, signature metabolites in cancers play very important roles in tumor progression and can be used in diagnosis and prognosis of cancers.

Keywords

Tumorigenesis Metabolism disorder Oncogene Metabolite Cancer treatment 

References

  1. Abidin AZ, Garassino MC, Califano R, Harle A, Blackhall F (2010) Targeted therapies in small cell lung cancer: a review. Ther Adv Med Oncol 2(1):25–37PubMedPubMedCentralCrossRefGoogle Scholar
  2. Adams S et al (2012) The kynurenine pathway in brain tumor pathogenesis. Cancer Res 72:5649–5657PubMedCrossRefGoogle Scholar
  3. Agostino C et al (2006) Accuracy of ultrasonography, spiral CT, magnetic resonance, and alpha-fetoprotein in diagnosing hepatocellular carcinoma: a systematic review. Am J Gastroenterol 101(3):513CrossRefGoogle Scholar
  4. Aisen AM, Martel W, Braunstein EM, Mcmillin KI, Phillips WA, Kling TF (1986) MRI and CT evaluation of primary bone and soft-tissue tumors. Year Book Medical Publishers, ChicagoCrossRefGoogle Scholar
  5. Akram M (2013) Mini-review on glycolysis and cancer. J Cancer Educ 28:454–457PubMedCrossRefGoogle Scholar
  6. Ali D et al (2010) Identification of novel epigenetic biomarkers in colorectal cancer, GLDC and PPP1R14A. Eur J Cancer 8:175–175CrossRefGoogle Scholar
  7. Amelio I et al (2014) Serine and glycine metabolism in cancer. Trends Biochem Sci 39:191–198PubMedPubMedCentralCrossRefGoogle Scholar
  8. Aronson JK (1999) Biomarkers and surrogate endpoints. Br J Clin Pharmacol 6(4):179Google Scholar
  9. Baggetto LG (1992) Deviant energetic metabolism of glycolytic cancer cells. Biochimie 74:959–974PubMedCrossRefGoogle Scholar
  10. Balliet RM et al (2011) Mitochondrial oxidative stress in cancer-associated fibroblasts drives lactate production, promoting breast cancer tumor growth. Cell Cycle 10:4065–4073PubMedPubMedCentralCrossRefGoogle Scholar
  11. Bao B et al (2011) Anti-tumor activity of a novel compound-CDF is mediated by regulating miR-21, miR-200, and PTEN in pancreatic cancer. PLoS One 6:e17850PubMedPubMedCentralCrossRefGoogle Scholar
  12. Barger JF et al (2013) S6K1 determines the metabolic requirements for BCR-ABL survival. Oncogene 32:453–461PubMedCrossRefGoogle Scholar
  13. Bensaad K et al (2006) TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell 126:107–120CrossRefGoogle Scholar
  14. Berndt B et al (2013) Cell fusion is a potent inducer of aneuploidy and drug resistance in tumor cell normal cell hybrids. Crit Rev Oncog 18:97–113PubMedCrossRefGoogle Scholar
  15. Biaglow JE, Miller RA (2005) The thioredoxin reductase/thioredoxin system: novel redox targets for cancer therapy. Cancer Biol Ther 4(1):13–20CrossRefGoogle Scholar
  16. Blair DG et al (1981) Activation of the transforming potential of a normal cell sequence: a molecular model for oncogenesis. Science 212:941–943PubMedCrossRefGoogle Scholar
  17. Bleeker FE, Lamba S, Leenstra S, Troost D, Hulsebos T, Vandertop WP, Frattini M, Molinari F, Knowles M, Cerrato A (2010) IDH1 mutations at residue p.R132 (IDH1(R132)) occur frequently in high-grade gliomas but not in other solid tumors. Hum Mutat 30(1):7–11CrossRefGoogle Scholar
  18. Bobarykina AY, Minchenko DO, Opentanova IL, Moenner M, Caro J, Esumi H, Minchenko OH (2006) Hypoxic regulation of PFKFB-3 and PFKFB-4 gene expression in gastric and pancreatic cancer cell lines and expression of PFKFB genes in gastric cancers. Acta Biochim Pol 53(4):789–799PubMedGoogle Scholar
  19. Bonnet S, Archer SL, Allalunisturner J, Haromy A, Beaulieu C, Thompson R, Lee CT, Lopaschuk GD, Puttagunta L, Bonnet S (2007) A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth. Cancer Cell 11(1):37–51PubMedCrossRefGoogle Scholar
  20. Borodovsky A, Seltzer MJ, Riggins GJ (2012) Altered cancer cell metabolism in gliomas with mutant IDH1 or IDH2. Curr Opin Oncol 24(1):83–89PubMedPubMedCentralCrossRefGoogle Scholar
  21. Bralten LB et al (2011) IDH1 R132H decreases proliferation of glioma cell lines in vitro and in vivo. Ann Neurol 69:455–463PubMedCrossRefGoogle Scholar
  22. Branford S et al (2003) Detection of BCR-ABL mutations in patients with CML treated with imatinib is virtually always accompanied by clinical resistance, and mutations in the ATP phosphate-binding loop (P-loop) are associated with a poor prognosis. Blood 102:276–283PubMedCrossRefGoogle Scholar
  23. Buttar NS et al (2014) Aspirin mediated downregulation of Warburg kinase AKT1 in patients with Barrett’s esophagus: implications in neoplastic transformation. Cancer Prev Res 5:PR-03-PR-03Google Scholar
  24. Cairns RA et al (2011) Regulation of cancer cell metabolism. Nat Rev Cancer 11:85–95CrossRefGoogle Scholar
  25. Calin GA et al (2008) MiR-15a and miR-16-1 cluster functions in human leukemia. Proc Natl Acad Sci U S A 105:5166–5171PubMedPubMedCentralCrossRefGoogle Scholar
  26. Camarero N et al (2006) Ketogenic HMGCS2 Is a c-Myc target gene expressed in differentiated cells of human colonic epithelium and down-regulated in colon cancer. Mol Cancer Res 4:645–653CrossRefGoogle Scholar
  27. Carrola J, Rocha CM, Barros AS, Gil AM, Goodfellow BJ, Carreira IM, Bernardo J, Gomes A, Sousa V, Carvalho L (2011) Metabolic signatures of lung cancer in biofluids: NMR-based metabonomics of urine. J Proteome Res 10(1):221PubMedCrossRefGoogle Scholar
  28. Chaffer CL et al (2013) Poised chromatin at the ZEB1 promoter enables breast cancer cell plasticity and enhances tumorigenicity. Cell 154:61–74PubMedPubMedCentralCrossRefGoogle Scholar
  29. Chaneton B, Gottlieb E (2012) Rocking cell metabolism: revised functions of the key glycolytic regulator PKM2 in cancer. Trends Biochem Sci 37:309–316PubMedCrossRefGoogle Scholar
  30. Chang Y et al (2014) AMPK and metabolisms of glucose and lipid. Adv Mater Res 887:547–550CrossRefGoogle Scholar
  31. Chen XQ, Stroun M, Anker P (2007) Cancer diagnosis method. USA Patent 7163789Google Scholar
  32. Chen Q et al (2015) The transcription factor C-Myc suppresses MiR-23b and MiR-27b transcription during fetal distress and increases the sensitivity of neurons to hypoxia-induced apoptosis. PLoS One 10:e0120217PubMedPubMedCentralCrossRefGoogle Scholar
  33. Chen Y, Zhang S, Wang Q, Zhang X (2017) Tumor-recruited M2 macrophages promote gastric and breast cancer metastasis via M2 macrophage-secreted CHI3L1 protein. J Hematol Oncol 10:36.  https://doi.org/10.1186/s13045-017-0408-0 CrossRefPubMedPubMedCentralGoogle Scholar
  34. Chiavarina B et al (2011) Pyruvate kinase expression (PKM1 and PKM2) in cancer-associated fibroblasts drives stromal nutrient production and tumor growth. Cancer Biol Ther 12:1101–1113PubMedPubMedCentralCrossRefGoogle Scholar
  35. Chiba T et al (2006) Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties. Hepatology 44:240–251PubMedCrossRefGoogle Scholar
  36. Chowdhury R, Yeoh KK, Tian YM, Hillringhaus L, Bagg EA, Rose NR, Leung IKH, Li XS, Woon ECY, Yang M (2011) The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases. EMBO Rep 12(5):463–469PubMedPubMedCentralCrossRefGoogle Scholar
  37. Ciavardelli D, Rossi C, Barcaroli D, Volpe S, Consalvo A, Zucchelli M, Cola AD, Scavo E, Carollo R, D’agostino D (2014) Breast cancer stem cells rely on fermentative glycolysis and are sensitive to 2-deoxyglucose treatment. Cell Death Dis 5(7):e1336PubMedPubMedCentralCrossRefGoogle Scholar
  38. Cioce M et al (2014) Metformin-induced metabolic reprogramming of chemoresistant ALDH breast cancer cells. Oncotarget 5:4129–4143PubMedPubMedCentralCrossRefGoogle Scholar
  39. Clem B, Telang S, Clem A, Yalcin A, Meier J, Simmons A, Rasku MA, Arumugam S, Dean WL, Eaton J (2008) Small-molecule inhibition of 6-phosphofructo-2-kinase activity suppresses glycolytic flux and tumor growth. Mol Cancer Ther 7(1):110PubMedCrossRefGoogle Scholar
  40. Clem BF, O’neal J, Tapolsky G, Clem AL, Imbert-Fernandez Y, Klarer AC, Redman R, Miller DM, Trent JO (2013) Targeting 6-phosphofructo-2-kinase (PFKFB3) as a therapeutic strategy against cancer. Mol Cancer Ther 12(8):1461–1470PubMedPubMedCentralCrossRefGoogle Scholar
  41. Coleman MC et al (2004) Inhibition of glucose metabolism in pancreatic cancer induces cytotoxicity via metabolic oxidative stress. J Am Coll Surg 199:24–24CrossRefGoogle Scholar
  42. Collier JJ et al (2003) c-Myc is required for the glucose-mediated induction of metabolic enzyme genes. J Biol Chem 278:6588–6595PubMedCrossRefGoogle Scholar
  43. Cory JG, Cory AH (2006) Critical roles of glutamine as nitrogen donors in purine and pyrimidine nucleotide synthesis: asparaginase treatment in childhood acute lymphoblastic leukemia. Vivo 20(5):587–589Google Scholar
  44. Costello LC, Franklin RB (2005) ‘Why do tumour cells glycolyse?’: from glycolysis through citrate to lipogenesis. Mol Cell Biochem 280(1–2):1–8PubMedPubMedCentralCrossRefGoogle Scholar
  45. Curry JM et al (2013) Cancer metabolism, stemness and tumor recurrence. Cell Cycle 12:1371–1384PubMedPubMedCentralCrossRefGoogle Scholar
  46. Dalerba P et al (2007) Cancer Stem cells: models and concepts. Annu Rev Med 58:267–284PubMedCrossRefGoogle Scholar
  47. Dang CV (2010) Rethinking the Warburg effect with Myc micromanaging glutamine metabolism. Cancer Res 70:859–862PubMedPubMedCentralCrossRefGoogle Scholar
  48. Dang CV (2013) MYC, metabolism, cell growth, and tumorigenesis. Cold Spring Harb Perspect Med 3:341–350CrossRefGoogle Scholar
  49. Dang L, White DW, Gross S, Bennett BD, Bittinger MA et al (2010) Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462(7274):739–744CrossRefGoogle Scholar
  50. Dang L, Yen K, Attar EC (2016) IDH mutations in cancer and progress toward development of targeted therapeutics. Ann Oncol 27(4):599–608PubMedCrossRefGoogle Scholar
  51. Daye D, Wellen KE (2012) Metabolic reprogramming in cancer: unraveling the role of glutamine in tumorigenesis. Semin Cell Dev Biol 23:362–369PubMedCrossRefGoogle Scholar
  52. Dayton TL et al (2016) PKM2, cancer metabolism, and the road ahead. EMBO Rep 17:1721–1730PubMedPubMedCentralCrossRefGoogle Scholar
  53. Demetrius LA et al (2010) Cancer proliferation and therapy: the Warburg effect and quantum metabolism. Theor Biol Med Model 7:2–19PubMedPubMedCentralCrossRefGoogle Scholar
  54. Deshmukh A et al (2016) Cancer stem cell metabolism: a potential target for cancer therapy. Mol Cancer 15(1):69–78PubMedPubMedCentralCrossRefGoogle Scholar
  55. Di TL et al (2007) Diagnostic value of HSP70, glypican 3, and glutamine synthetase in hepatocellular nodules in cirrhosis. Hepatology 45(3):725–734CrossRefGoogle Scholar
  56. Diazruiz R et al (2011) The Warburg and Crabtree effects: on the origin of cancer cell energy metabolism and of yeast glucose repression. Biochim Biophys Acta 1807:568–576CrossRefGoogle Scholar
  57. Dong G et al (2016) PKM2 and cancer: the function of PKM2 beyond glycolysis. Oncol Lett 11:1980–1986PubMedPubMedCentralCrossRefGoogle Scholar
  58. Eason K, Sadanandam A (2016) Molecular or metabolic reprograming: what triggers tumor subtypes? Cancer Res 76:5195–5200PubMedCrossRefGoogle Scholar
  59. Emadi A, Jun SA, Tsukamoto T, Fathi AT, Minden MD, Dang CV (2014) Inhibition of glutaminase selectively suppresses the growth of primary acute myeloid leukemia cells with IDH mutations. Exp Hematol 42(4):247–251PubMedCrossRefGoogle Scholar
  60. Eng CH, Abraham RT (2011) The autophagy conundrum in cancer: influence of tumorigenic metabolic reprogramming. Oncogene 30:4687–4696PubMedCrossRefGoogle Scholar
  61. Fan J, Kang HB, Shan C, Elf S, Lin R, Xie J, Gu TL, Aguiar M, Lonning S, Chung TW (2011) Tyr-301 phosphorylation inhibits pyruvate dehydrogenase by blocking substrate binding and promotes the Warburg effect. J Biol Chem 289(38):26533CrossRefGoogle Scholar
  62. Fantin VR, Stpierre J, Leder P (2006) Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer Cell 9(6):425–434PubMedCrossRefGoogle Scholar
  63. Fantin VR et al (2010) Cancer-associated metabolite 2-hydroxyglutarate accumulates in AML with IDH1/2 mutations. Cancer Res 70:5452–5452CrossRefGoogle Scholar
  64. Fathi AT, Sadrzadeh H, Borger DR, Ballen KK, Amrein PC, Attar EC, Foster J, Burke M, Lopez HU, Matulis CR (2012) Prospective serial evaluation of 2-hydroxyglutarate, during treatment of newly diagnosed acute myeloid leukemia, to assess disease activity and therapeutic response. Blood 120(23):4649PubMedCrossRefGoogle Scholar
  65. Fei X et al (2012) MicroRNA-195-5p suppresses glucose uptake and proliferation of human bladder cancer T24 cells by regulating GLUT3 expression. FEBS Lett 586:392–397PubMedCrossRefGoogle Scholar
  66. Ferreira LM et al (2012) Metabolic reprogramming of the tumor. Oncogene 31:3999–4011PubMedCrossRefGoogle Scholar
  67. Fiehn O (2002) Metabolomics--the link between genotypes and phenotypes. Plant Mol Biol 48(2):155–171PubMedCrossRefGoogle Scholar
  68. Flavahan WA, Wu Q, Hitomi M, Rahim N, Kim Y, Sloan AE, Weil RJ, Nakano I, Sarkaria JN, Stringer BW (2013) Brain tumor initiating cells adapt to restricted nutrition through preferential glucose uptake. Nat Neurosci 16(10):1373–1382PubMedPubMedCentralCrossRefGoogle Scholar
  69. Fogarty S, Hardie DG (2010) Development of protein kinase activators: AMPK as a target in metabolic disorders and cancer. Biochim Biophys Acta Proteins Proteomics 1804:581–591CrossRefGoogle Scholar
  70. Fong LY et al (2017) Integration of metabolomics, transcriptomics, and microRNA expression profiling reveals a miR-143-HK2-glucose network underlying zinc-deficiency-associated esophageal neoplasia. Oncotarget 8:81910–81925PubMedPubMedCentralGoogle Scholar
  71. Fox MP et al (2011) C-Myc overexpression drives aerobic glycolysis independent of anaplerotic pyruvate carboxylase expression in non small cell lung cancer. J Am Coll Surg 213:S39–S39CrossRefGoogle Scholar
  72. Furuta E et al (2010) Metabolic genes in cancer: their roles in tumor progression and clinical implications. Biochim Biophys Acta Rev Cancer 1805:141–152CrossRefGoogle Scholar
  73. Galbiati F et al (2001) Caveolin-1 expression negatively regulates cell cycle progression by inducing G0/G1 arrest via a p53/p21WAF1/Cip1-dependent mechanism. Mol Biol Cell 12:2229–2244PubMedPubMedCentralCrossRefGoogle Scholar
  74. Galoian K et al (2009) Myc-oncogene inactivating effect by Proline Rich Polypeptide (PRP-1) in chondrosarcoma JJ012 cells. Neurochem Res 34:379–385PubMedCrossRefGoogle Scholar
  75. Galon J et al (2012) Cancer classification using the Immunoscore: a worldwide task force. J Transl Med 10:205–213PubMedPubMedCentralCrossRefGoogle Scholar
  76. Gao N et al (2004) G1 cell cycle progression and the expression of G1 cyclins are regulated by PI3K/AKT/mTOR/p70S6K1 signaling in human ovarian cancer cells. Am J Phys Cell Phys 287:C281CrossRefGoogle Scholar
  77. Gao P, Tchernyshyov I, Chang TC, Lee YS, Kita K et al (2009) c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature 458(7239):762–765PubMedPubMedCentralCrossRefGoogle Scholar
  78. Gao H, Lu Q, Liu X, Cong H, Zhao L, Wang H, Lin D (2010) Application of 1H NMR-based metabonomics in the study of metabolic profiling of human hepatocellular carcinoma and liver cirrhosis. Cancer Sci 100(4):782–785CrossRefGoogle Scholar
  79. Garcia E, Andrews C, Hua J, Kim HL, Sukumaran DK, Szyperski T, Odunsi K (2011) Diagnosis of early stage ovarian cancer by 1H NMR metabonomics of serum explored by use of a micro-flow NMR probe. J Proteome Res 10(4):1765–1771PubMedPubMedCentralCrossRefGoogle Scholar
  80. Gatenby RA, Gillies RJ (2004) Why do cancers have high aerobic glycolysis? Nat Rev Cancer 4:891–899PubMedCrossRefGoogle Scholar
  81. Gershon TR, Crowther AJ, Andrey T, Idoia G, Ryan A, Yuan H, Ryan MC, Jeffrey M, James O, Mohanish D (2013) Hexokinase-2-mediated aerobic glycolysis is integral to cerebellar neurogenesis and pathogenesis of medulloblastoma. Cancer Metab 1(1):2PubMedPubMedCentralCrossRefGoogle Scholar
  82. Gottlieb E, Tomlinson IP (2005) Mitochondrial tumour suppressors: a genetic and biochemical update. Nat Rev Cancer 5(11):857–866PubMedPubMedCentralCrossRefGoogle Scholar
  83. Gottlob K et al (2001) Inhibition of early apoptotic events by Akt/PKB is dependent on the first committed step of glycolysis and mitochondrial hexokinase. Genes Dev 15:1406–1418PubMedPubMedCentralCrossRefGoogle Scholar
  84. Gottschalk S et al (2004) Imatinib (STI571)-mediated changes in glucose metabolism in human leukemia BCR-ABL-positive cells. Clin Cancer Res 10:6661–6668PubMedCrossRefGoogle Scholar
  85. Gowda P et al (2018) Mutant IDH1 disrupts PKM2-β-catenin-BRG1 transcriptional network driven CD47 expression. Mol Cell Biol 38.  https://doi.org/10.1128/MCB.00001-18
  86. Granchi C et al (2011) Discovery of N-hydroxyindole-based inhibitors of human lactate dehydrogenase isoform A (LDH-A) as starvation agents against cancer cells. J Med Chem 54:1599–1612PubMedCrossRefGoogle Scholar
  87. Gwak H et al (2015) Cancer-specific interruption of glucose metabolism by resveratrol is mediated through inhibition of Akt/GLUT1 axis in ovarian cancer cells. Mol Carcinog 54(12):1529–1540PubMedCrossRefGoogle Scholar
  88. Hakim M, Billan S, Tisch U, Peng G, Dvrokind I, Marom O, Abdahbortnyak R, Kuten A, Haick H (2011) Diagnosis of head-and-neck cancer from exhaled breath. Br J Cancer 104(10):1649–1655PubMedPubMedCentralCrossRefGoogle Scholar
  89. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674PubMedPubMedCentralCrossRefGoogle Scholar
  90. Haynes HR et al (2014) Prognostic and predictive biomarkers in adult and pediatric gliomas: toward personalized treatment. Front Oncol 4:47–59PubMedPubMedCentralCrossRefGoogle Scholar
  91. He TL et al (2005) The c-Myc–LDHA axis positively regulates aerobic glycolysis and promotes tumor progression in pancreatic cancer. Med Oncol 32(7):187–202CrossRefGoogle Scholar
  92. Hebertchatelain E et al (2012) Preservation of NADH ubiquinone- oxidoreductase activity by Src kinase-mediated phosphorylation of NDUFB10. BBA-Bioenergetics 1817:718–725CrossRefGoogle Scholar
  93. Heng B et al (2016) Understanding the role of the kynurenine pathway in human breast cancer immunobiology. Oncotarget 7:6506–6520PubMedGoogle Scholar
  94. Hensley CT, Wasti AT, Deberardinis RJ (2013) Glutamine and cancer: cell biology, physiology, and clinical opportunities. J Clin Investig 123(9):3678–3684PubMedCrossRefGoogle Scholar
  95. Hirsch HA et al (2009) Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission. Cancer Res 69:7507–7511PubMedPubMedCentralCrossRefGoogle Scholar
  96. Hoon H, Xuan YI, Bae KY, Gwang L, Wooyoung S, Yun J, In-Hye H, Han SU (2013) Expression of pyruvate dehydrogenase kinase-1 in gastric cancer as a potential therapeutic target. Int J Oncol 42(1):44–54CrossRefGoogle Scholar
  97. Hresko RC, Hruz PW (2011) HIV protease inhibitors act as competitive inhibitors of the cytoplasmic glucose binding site of GLUTs with differing affinities for GLUT1 and GLUT4. PLoS One 6(9):e25237PubMedPubMedCentralCrossRefGoogle Scholar
  98. Hu ZY et al (2014) Glycolytic genes in cancer cells are more than glucose metabolic regulators. J Mol Med 92:1009–1009CrossRefGoogle Scholar
  99. Huang R et al (2017) Circular RNA HIPK2 regulates astrocyte activation via cooperation of autophagy and ER stress by targeting MIR124–2HG. Autophagy 13:1–20CrossRefGoogle Scholar
  100. Ibsen KH (1961) The Crabtree effect: a review. Cancer Res 21(21):829PubMedGoogle Scholar
  101. Jaekyoung S, Lyssiotis CA, Ying H, Wang X, Hua S, Matteo L, Perera RM, Ferrone CR, Edouard M, Ng SC (2013) Glutamine supports pancreatic cancer growth through a Kras-regulated metabolic pathway. Nature 496(7443):101–105CrossRefGoogle Scholar
  102. Jain M, Nilsson R, Sharma S, Madhusudhan N, Kitami T, Souza AL, Kafri R, Kirschner MW, Clish CB, Mootha VK (2012) Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation. Science 336(6084):1040–1044PubMedPubMedCentralCrossRefGoogle Scholar
  103. Jha MK, Suk K (2013) Pyruvate dehydrogenase kinase as a potential therapeutic target for malignant gliomas. Brain Tumor Res Treat 1(2):57–63PubMedPubMedCentralCrossRefGoogle Scholar
  104. Jiang W et al (2015) FOXM1-LDHA signaling promoted gastric cancer glycolytic phenotype and progression. Int J Clin Exp Pathol 8:6756–6763PubMedPubMedCentralGoogle Scholar
  105. Jing L et al (2017) Induced-decay of glycine decarboxylase transcripts as an anticancer therapeutic strategy for non-small-cell lung carcinoma. Mol Ther Nucleic Acids 9:263–273CrossRefGoogle Scholar
  106. Jobard E, Pontoizeau C, Blaise BJ, Bachelot T, Trédan O (2014) A serum nuclear magnetic resonance-based metabolomic signature of advanced metastatic human breast cancer. Cancer Lett 343(1):33–41PubMedCrossRefGoogle Scholar
  107. Jones RG, Thompson CB (2009) Tumor suppressors and cell metabolism: a recipe for cancer growth. Genes Dev 23(5):537–548PubMedPubMedCentralCrossRefGoogle Scholar
  108. Jung SY, Jeon HK, Choi JS, Kim YJ (2012) Reduced expression of FASN through SREBP-1 down-regulation is responsible for hypoxic cell death in HepG2 cells. J Cell Biochem 113(12):3730–3739PubMedCrossRefGoogle Scholar
  109. Kang MR, Kim MS, Oh JE, Kim YR, Song SY, Seo SI, Lee JY, Yoo NJ, Lee SH (2010) Mutational analysis of IDH1 codon 132 in glioblastomas and other common cancers. Int J Cancer 125(2):353–355CrossRefGoogle Scholar
  110. Kapiteijn E et al (2001) Mechanisms of oncogenesis in colon versus rectal cancer. J Pathol 195:171–178PubMedCrossRefPubMedCentralGoogle Scholar
  111. Keller KE et al (2014) SAICAR induces protein kinase activity of PKM2 that is necessary for sustained proliferative signaling of cancer cells. Mol Cell 53:700–709PubMedPubMedCentralCrossRefGoogle Scholar
  112. Kim JW et al (2007) 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 27:7381–7393PubMedPubMedCentralCrossRefGoogle Scholar
  113. Kinzler KW (1998) ONCOGENESIS: landscaping the cancer terrain. Science 280:1036–1037PubMedCrossRefPubMedCentralGoogle Scholar
  114. Klepper J, Voit T (2002) Facilitated glucose transporter protein type 1 (GLUT1) deficiency syndrome: impaired glucose transport into brain-- a review. Eur J Pediatr 161(6):295–304PubMedCrossRefPubMedCentralGoogle Scholar
  115. Koseki J et al (2015) Mathematical analysis predicts imbalanced IDH1/2 expression associates with 2-HG-inactivating Î2-oxygenation pathway in colorectal cancer. Int J Oncol 46:1181–1191PubMedCrossRefPubMedCentralGoogle Scholar
  116. Koster R et al (2017) Genome-wide association study identifies the GLDC/IL33 locus associated with survival of osteosarcoma patients. Int J Cancer 142:1594–1601PubMedPubMedCentralCrossRefGoogle Scholar
  117. Koukourakis MI, Giatromanolaki A, Simopoulos C, Polychronidis A, Sivridis E (2005) Lactate dehydrogenase 5 (LDH5) relates to up-regulated hypoxia inducible factor pathway and metastasis in colorectal cancer. Clin Exp Metastasis 22(1):25–30PubMedCrossRefGoogle Scholar
  118. Kubo Y et al (2014) Molecular tumorigenesis of the skin. J Med Investig 61:7–14CrossRefGoogle Scholar
  119. Kubota Y et al (1987) The enhanced 32P labeling of CDP-diacylglycerol in c-myc gene expressed human kidney cancer cells. FEBS Lett 212:159–162PubMedCrossRefGoogle Scholar
  120. Kumar B, Bamezai RNK (2015) Moderate DNA damage promotes metabolic flux into PPP via PKM2 Y-105 phosphorylation: a feature that favours cancer cells. Mol Biol Rep 42:1317–1321PubMedCrossRefGoogle Scholar
  121. Latham T et al (2012) Lactate, a product of glycolytic metabolism, inhibits histone deacetylase activity and promotes changes in gene expression. Nucleic Acids Res 40:4794–4803PubMedPubMedCentralCrossRefGoogle Scholar
  122. Le MT et al (2009) MicroRNA-125b is a novel negative regulator of p53. Genes Dev 23:862–876PubMedPubMedCentralCrossRefGoogle Scholar
  123. Le A, Lane AN, Hamaker M, Bose S, Gouw A, Barbi J, Tsukamoto T, Rojas CJ, Slusher BS, Zhang H (2012) Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B-cells. Cell Metab 15(1):110–121PubMedPubMedCentralCrossRefGoogle Scholar
  124. Lee EK et al (2010) Transgelin promotes migration and invasion of cancer stem cells. J Proteome Res 9:5108–5117PubMedCrossRefGoogle Scholar
  125. Lee JEA et al (2014) MYC function and regulation in flies: how Drosophila has enlightened MYC cancer biology. Aims Energy 1:81–98Google Scholar
  126. Leerapun A et al (2007) The utility of AFP-L3% in the diagnosis of hepatocellular carcinoma: evaluation in a US referral population. Clinical Gastroenterology & Hepatology 5(3):267–267CrossRefGoogle Scholar
  127. Levine AJ, Puzio-Kuter AM (2010) The control of the metabolic switch in cancersbyoncogenes and tumor suppressor genes. Science 330:1340–1344PubMedCrossRefGoogle Scholar
  128. Li C et al (2006) Identification of pancreatic cancer stem cells. J Surg Res 130:194–195Google Scholar
  129. Li W et al (2016) Resveratrol inhibits Hexokinases II mediated glycolysis in non-small cell lung cancer via targeting Akt signaling pathway. Exp Cell Res 349:320–327PubMedCrossRefPubMedCentralGoogle Scholar
  130. Liang Q, Yu Q, Wu H, Zhu Y, Zhang A (2014) Metabolite fingerprint analysis of cervical cancer using LC-QTOF/MS and multivariate data analysis. Anal Methods 6(12):3937–3942CrossRefGoogle Scholar
  131. Liao Y (2014) Akt signaling pathway in the regulation of glucose metabolism in cancer cells. Electron J Metab Nutr Cancer 1(3):61–69Google Scholar
  132. Liberti MV, Locasale JW (2016) The Warburg effect: how does it benefit cancer cells? Trends Biochem Sci 41:211–218PubMedPubMedCentralCrossRefGoogle Scholar
  133. Ligor T, Szeliga J, Jackowski M, Buszewski B (2007) Preliminary study of volatile organic compounds from breath and stomach tissue by means of solid phase microextraction and gas chromatography-mass spectrometry. J Breath Res 1(1):016001PubMedCrossRefPubMedCentralGoogle Scholar
  134. Lin B, Xu LI, Zhang H (2015) Potential therapeutic target of energy metabolism for cancer. Chem Life 35(1):45–50Google Scholar
  135. Lin CP et al (2012) The emerging functions of the p53-miRNA network in stem cell biology. Cell Cycle 11:2063–2072PubMedPubMedCentralCrossRefGoogle Scholar
  136. Lincet H, Icard P (2014) How do glycolytic enzymes favour cancer cell proliferation by nonmetabolic functions? Oncogene 34:3751–3759PubMedCrossRefPubMedCentralGoogle Scholar
  137. Liu YC et al (2008) Global regulation of nucleotide biosynthetic genes by c-Myc. PLoS One 3:e2722PubMedPubMedCentralCrossRefGoogle Scholar
  138. Liu T, Kishton RJ, Macintyre AN, Gerriets VA, Xiang H, Liu X, Abel ED, Rizzieri D, Locasale JW, Rathmell JC (2014) Glucose transporter 1-mediated glucose uptake is limiting for B-cell acute lymphoblastic leukemia anabolic metabolism and resistance to apoptosis. Cell Death Dis 5(11):e1470PubMedPubMedCentralCrossRefGoogle Scholar
  139. Liu F et al (2017) PKM2 methylation by CARM1 activates aerobic glycolysis to promote tumorigenesis. Nat Cell Biol 19:1358–1370PubMedPubMedCentralCrossRefGoogle Scholar
  140. Liu Q, Huang Q (2015) Characteristics of energy metabolism of tumor cells and its significance. Chem Life 35(3):387–391Google Scholar
  141. Lock R et al (2011) Autophagy facilitates glycolysis during Ras-mediated oncogenic transformation. Mol Biol Cell 22:165–178PubMedPubMedCentralCrossRefGoogle Scholar
  142. Loiseau AM, Rousseau GG, Hue L (1985) Fructose 2,6-bisphosphate and the control of glycolysis by glucocorticoids and by other agents in rat hepatoma cells. Cancer Res 45(9):4263–4269PubMedPubMedCentralGoogle Scholar
  143. Lopiccolo J et al (2008) Targeting the PI3K/Akt/mTOR pathway: effective combinations and clinical considerations. Drug Resist Updat 11:32–50PubMedCrossRefPubMedCentralGoogle Scholar
  144. Lu H et al (2010) MicroRNA-223 regulates Glut4 expression and cardiomyocyte glucose metabolism. Cardiovasc Res 86:410–420PubMedCrossRefPubMedCentralGoogle Scholar
  145. Lunt SY et al (2011) Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Annu Rev Cell Dev Biol 27:441–464CrossRefGoogle Scholar
  146. Macheda ML et al (2005) Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer. J Cell Physiol 202:654–662PubMedCrossRefPubMedCentralGoogle Scholar
  147. Macintyre AN, Gerriets VA, Nichols AG, Michalek RD, Rudolph MC, Deoliveira D, Anderson SM, Abel ED, Chen BJ, Hale LP (2014) The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function. Cell Metab 20(1):61–72PubMedPubMedCentralCrossRefGoogle Scholar
  148. Malik ST et al (1991) Antitumor activity of γ-interferon in ascitic and solid tumor models of human ovarian cancer. Cancer Res 51:6643–6649PubMedPubMedCentralGoogle Scholar
  149. Manerba M, Vettraino M, Fiume L, Sartini A, Giacomini E, Buonfiglio R, Roberti M, Recanatini M (2012) Galloflavin (CAS 568-80-9): a novel inhibitor of lactate dehydrogenase. ChemMedChem 7(2):311–317PubMedCrossRefPubMedCentralGoogle Scholar
  150. Mao Y et al (2010) Golgi protein 73 (GOLPH2) is a valuable serum marker for hepatocellular carcinoma. Gut 59(12):1687–1693PubMedCrossRefGoogle Scholar
  151. Mardis ER, Ding L, Dooling DJ, Larson DE, Mclellan MD, Chen K, Koboldt DC, Fulton RS, Delehaunty KD, Mcgrath SD (2009) Recurring mutations found by sequencing an acute myeloid leukemia genome. N Engl J Med 361(11):1058–1066PubMedPubMedCentralCrossRefGoogle Scholar
  152. Marín-Hernández A et al (2011) Modeling cancer glycolysis. Biochim Biophys Acta (BBA) – Bioenergetics 1807:755–767CrossRefGoogle Scholar
  153. Marrero JA et al (2005) GP73, a resident Golgi glycoprotein, is a novel serum marker for hepatocellular carcinoma. J Hepatol 43(6):1007–1012PubMedCrossRefGoogle Scholar
  154. Martinezoutschoorn UE et al (2011) Ketones and lactate increase cancer cell “stemness,” driving recurrence, metastasis and poor clinical outcome in breast cancer: achieving personalized medicine via Metabolo-Genomics. Cell Cycle 10:1271–1286CrossRefGoogle Scholar
  155. Mathews EH, Liebenberg L (2013) Is knowledge of brain metabolism the key to treatinghighly glycolytic cancers and metastases? Neuro-Oncology 15:649–649PubMedPubMedCentralCrossRefGoogle Scholar
  156. Mathews EH et al (2011) High-glycolytic cancers and their interplay with the body’s glucose demand and supply cycle. Med Hypotheses 76:157–165PubMedCrossRefGoogle Scholar
  157. Mcbrayer SK, Cheng JC, Singhal S, Krett NL, Rosen ST, Shanmugam M (2012) Multiple myeloma exhibits novel dependence on GLUT4, GLUT8, and GLUT11: implications for glucose transporter-directed therapy. Blood 119(20):4686–4697PubMedPubMedCentralCrossRefGoogle Scholar
  158. Mccartan D et al (2012) Global characterization of the SRC-1 transcriptome identifies ADAM22 as an ER-independent mediator of endocrine resistant breast cancer. Cancer Res 72:220–229PubMedCrossRefGoogle Scholar
  159. Meadows AL et al (2008) Metabolic and morphological differences between rapidly proliferating cancerous and normal breast epithelial cells. Biotechnol Prog 24:334–341PubMedCrossRefPubMedCentralGoogle Scholar
  160. Mennigen JA (2016) Micromanaging metabolism-a role for miRNAs in teleost energy metabolism. Comp Biochem Physiol 199:115–125CrossRefGoogle Scholar
  161. Mentis AF, Kararizou E (2010) Metabolism and cancer: an up-to-date review of a mutual connection. Asian Pac J Cancer Prev 11(6):1437PubMedPubMedCentralGoogle Scholar
  162. Migneco G et al (2010) Glycolytic cancer associated fibroblasts promote breast cancer tumor growth, without a measurable increase in angiogenesis: evidence for stromal-epithelial metabolic coupling. Cell Cycle 9:2412–2422PubMedCrossRefPubMedCentralGoogle Scholar
  163. Min HY, Lee HY (2018) Oncogene-driven metabolic alterations in cancer. Biomol Ther 26:45–56CrossRefGoogle Scholar
  164. Min HL et al (2016) Epigenetic silencing of the putative tumor suppressor gene GLDC (Glycine Dehydrogenase) in gastric carcinoma. Anticancer Res 36:179–187PubMedPubMedCentralGoogle Scholar
  165. Miyahara T et al (2007) Phosphoinositide 3-kinase, Src, and Akt modulate acute ventilation-induced vascular permeability increases in mouse lungs. Am J Physiol Lung Cell Mol Physiol 293:11–21CrossRefGoogle Scholar
  166. Morrish F et al (2010) Myc-dependent mitochondrial generation of acetyl-CoA contributes to fatty acid biosynthesis and histone acetylation during cell cycle entry. J Biol Chem 285:36267–36274PubMedPubMedCentralCrossRefGoogle Scholar
  167. Münger K et al (2004) Mechanisms of human papillomavirus-induced oncogenesis. J Virol 78:11451–11460PubMedPubMedCentralCrossRefGoogle Scholar
  168. Murray GI et al (1993) Expression of xenobiotic metabolizing enzymes in breast cancer. J Pathol 169:347–353PubMedCrossRefPubMedCentralGoogle Scholar
  169. Narahara K, Kimura S, Kikkawa K, Takahashi Y, Wakita Y, Kasai R, Nagai S, Nishibayashi Y, Kimoto H (1985) Probable assignment of soluble isocitrate dehydrogenase (IDH1) to 2q33.3. Hum Genet 71(1):37PubMedCrossRefPubMedCentralGoogle Scholar
  170. Neiff N, Dhliwayo T, Suarez EA, Burgueno J, Trachsel S (2010) Advances in research of anti-tumor treatment with natural killer cells. J Chin PLA Postgrad Med Sch 29(6):669–690Google Scholar
  171. Nicklin P, Bergman P, Zhang B, Triantafellow E, Wang H, Nyfeler B, Yang H, Hild M, Kung C, Wilson C (2009) Bidirectional transport of amino acids regulates mTOR and autophagy. Cell 136(3):521–534PubMedPubMedCentralCrossRefGoogle Scholar
  172. Noh S et al (2014) Expression levels of serine/glycine metabolism-related proteins in triple negative breast cancer tissues. Tumour Biol 35:4457–4468PubMedCrossRefGoogle Scholar
  173. Oermann EK et al (2012) Alterations of metabolic genes and metabolites in cancer. Semin Cell Dev Biol 23:370–380PubMedPubMedCentralCrossRefGoogle Scholar
  174. Oh IU, Inazawa J, Kim YO, Song BJ, Huh TL (1996) Assignment of the human mitochondrial NADP + -specific isocitrate dehydrogenase (IDH2) gene to 15q26.1 by in situ hybridization. Genomics 38(1):104–106PubMedCrossRefGoogle Scholar
  175. Ono K (2011) MicroRNA links obesity and impaired glucose metabolism. Cell Res 21:864–866PubMedPubMedCentralCrossRefGoogle Scholar
  176. Ono M et al (1990) Measurement of immunoreactive prothrombin precursor and vitamin-Kdependent gamma-carboxylation in human hepatocellular carcinoma tissues: decreased carboxylation of prothrombin precursor as a cause of des-gamma-carboxyprothrombin synthesis. Tumour Biol 11(6):319–326PubMedCrossRefGoogle Scholar
  177. Pai YJ et al (2015) Glycine decarboxylase deficiency causes neural tube defects and features of non-ketotic hyperglycinemia in mice. Nat Commun 6:6388–6399PubMedPubMedCentralCrossRefGoogle Scholar
  178. Painter RB, Hughes WL (2010) Nucleic acid metabolism and the lethal effect of radiation on cultured human cells (HeLa). Ann N Y Acad Sci 95:960–968CrossRefGoogle Scholar
  179. Patra KC, Wang Q, Bhaskar PT, Miller L, Wang Z, Wheaton W, Chandel N, Laakso M, Muller WJ, Allen EL (2013) Hexokinase 2 is required for tumor initiation and maintenance and its systemic deletion is therapeutic in mouse models of cancer. Cancer Cell 24(2):213–228PubMedPubMedCentralCrossRefGoogle Scholar
  180. Peirispagès M et al (2016) Cancer stem cell metabolism. Breast Cancer Res 18:55–64CrossRefGoogle Scholar
  181. Peng G, Hakim M, Broza YY, Billan S, Abdah-Bortnyak R, Kuten A, Tisch U, Haick H (2010) Detection of lung, breast, colorectal, and prostate cancers from exhaled breath using a single array of nanosensors. Br J Cancer 103(4):542–551PubMedPubMedCentralCrossRefGoogle Scholar
  182. Phillips M, Cataneo RN, Saunders C, Hope P, Schmitt P, Wai J (2010) Volatile biomarkers in the breath of women with breast cancer. J Breath Res 4(2):026003PubMedCrossRefGoogle Scholar
  183. Pollard P, Wortham N, Tomlinson I (2003) The TCA cycle and tumorigenesis: the examples of fumarate hydratase and succinate dehydrogenase. Ann Med 35(8):634–635CrossRefGoogle Scholar
  184. Prasad N et al (2008) Crosstalk between metabolic and oncogenic pathways via SHIP2 inositol phosphatase. Cancer Res 68:68–78Google Scholar
  185. Qing G, Li B, Vu A, Skuli N, Walton Z, Liu X, Mayes P, Wise D, Thompson C, Maris J (2012) ATF4 regulates MYC -mediated neuroblastoma cell death upon glutamine deprivation. Cancer Cell 22(5):631–644PubMedPubMedCentralCrossRefGoogle Scholar
  186. Raimundo N, Baysal BE, Shadel GS (2011) Revisiting the TCA cycle: signaling to tumor formation. Trends Mol Med 17(11):641–649PubMedPubMedCentralCrossRefGoogle Scholar
  187. Resende C et al (2010) Genetic and epigenetic alteration in gastric carcinogenesis. Helicobacter 15:34–39PubMedCrossRefGoogle Scholar
  188. Ristow M (2006) Oxidative metabolism in cancer growth. Curr Opin Clin Nutr Metab Care 9:339–345PubMedCrossRefGoogle Scholar
  189. Robb MA, Mcinnes PM, Califf RM (2016) Biomarkers and surrogate endpoints. JAMA 315(11):1107–1108PubMedCrossRefGoogle Scholar
  190. Rosko JE (2006) From adult stem cells to cancer stem cells: Oct-4 Gene, cell-cell communication, and hormones during tumor promotion. Ann N Y Acad Sci 1089:36–58CrossRefGoogle Scholar
  191. Ross CD, Gomaa MA, Gillies E, Juengel R, Medina JE (2000) Tumor grade, microvessel density, and activities of malate dehydrogenase, lactate dehydrogenase, and hexokinase in squamous cell carcinoma. Otolaryngology--head and neck surgery. Off J Am Acad Otolaryngol-Head Neck Surg 122(2):195CrossRefGoogle Scholar
  192. Sahra IB et al (2010) The combination of metformin and 2 deoxyglucose inhibits autophagy and induces AMPK-dependent apoptosis in prostate cancer cells. Autophagy 6:670–671PubMedCrossRefGoogle Scholar
  193. Sampson VB et al (2007) MicroRNA let-7a down-regulates MYC and reverts MYC-induced growth in Burkitt lymphoma cells. Cancer Res 67:9762–9770PubMedCrossRefGoogle Scholar
  194. Sanyal S et al (2004) Polymorphisms in DNA repair and metabolic genes in bladder cancer. Carcinogenesis 25:729–734PubMedCrossRefGoogle Scholar
  195. Sasaki M et al (2012) IDH1(R132H) mutation increases murine haematopoietic progenitors and alters epigenetics. Nature 488:656–659PubMedPubMedCentralCrossRefGoogle Scholar
  196. Sciacovelli M et al (2014) The metabolic alterations of cancer cells. Methods Enzymol 542:1–23PubMedCrossRefGoogle Scholar
  197. Sebastian C (2014) Tracking down the origin of cancer: metabolic reprogramming as a driver of stemness and tumorigenesis. Crit Rev Oncog 19:363–382PubMedCrossRefGoogle Scholar
  198. Sedwick C (2015) Glycolytic cancer cells splice their way out of trouble. J Cell Biol 210:1037–1037PubMedCentralCrossRefPubMedGoogle Scholar
  199. Semenza GL (2008) Tumor metabolism: cancer cells give and take lactate. J Clin Investig 118:3835–3837PubMedGoogle Scholar
  200. Shah M, Allegrucci C (2013) Stem cell plasticity in development and cancer: epigenetic origin of cancer stem cells. Subcell Biochem 61(7):545–565PubMedCrossRefGoogle Scholar
  201. Shariff MIF, Gomaa AI, Cox IJ, Patel M, Williams HRT, Crossey MME, Thillainayagam AV, Thomas HC, Waked I, Khan SA (2011) Urinary metabolic biomarkers of hepatocellular carcinoma in an Egyptian population: a validation study. J Proteome Res 10(4):1828–1836PubMedCrossRefGoogle Scholar
  202. Shaw RJ (2006) Glucose metabolism and cancer. Curr Opin Cell Biol 18:598–608PubMedCrossRefGoogle Scholar
  203. Shen YC, Ou DL, Hsu C, Lin KL, Chang CY, Lin CY, Liu SH, Cheng AL (2013) Activating oxidative phosphorylation by a pyruvate dehydrogenase kinase inhibitor overcomes sorafenib resistance of hepatocellular carcinoma. Br J Cancer 108(1):72–81PubMedCrossRefGoogle Scholar
  204. Shieh GS et al (2016) Lactate promoting cancer stem cell phenotype and inducing epithelial-mesenchymal transition. Urol Sci 27:S2–S3CrossRefGoogle Scholar
  205. Shoemaker RH (2006) The NCI60 human tumour cell line anticancer drug screen. Nat Rev Cancer 6(10):813PubMedCrossRefGoogle Scholar
  206. Shroff EH et al (2015) MYC oncogene overexpression drives renal cell carcinoma in a mouse model through glutamine metabolism. Proc Natl Acad Sci U S A 112:6539–6544PubMedPubMedCentralCrossRefGoogle Scholar
  207. Singh SK et al (2004) Cancer stem cells in nervous system tumors. Oncogene 23:7267–7273PubMedCrossRefGoogle Scholar
  208. Smith TA (2000) Mammalian hexokinases and their abnormal expression in cancer. Br J Biomed Sci 57(2):170–178PubMedGoogle Scholar
  209. Son J, Lyssiotis CA, Ying H, Wang X, Hua S, Ligorio M, Perera RM, Ferrone CR, Mullarky E, Shyhchang N (2013) Glutamine supports pancreatic cancer growth through a Kras-regulated metabolic pathway. Nature 496(7443):101–105PubMedPubMedCentralCrossRefGoogle Scholar
  210. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RT, Li Y (2009) Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature 457(7231):910–914PubMedPubMedCentralCrossRefGoogle Scholar
  211. Srivastava NK, Pradhan S, Gowda GAN, Kumar R (2010) In vitro, high-resolution 1H and 31P NMR based analysis of the lipid components in the tissue, serum, and CSF of the patients with primary brain tumors: one possible diagnostic view. NMR Biomed 23(2):113–122PubMedGoogle Scholar
  212. Stacpoole PW, Nagaraja NV, Hutson AD (2003) Efficacy of dichloroacetate as a lactate-lowering drug. J Clin Pharmacol 43(7):683–691PubMedCrossRefGoogle Scholar
  213. Stratton MR (2011) Exploring the genomes of cancer cells: progress and promise. Science 331:1553–1558PubMedCrossRefGoogle Scholar
  214. Strimbu K, Tavel JA (2010) What are biomarkers? Curr Opin HIV AIDS 5(6):463–466PubMedPubMedCentralCrossRefGoogle Scholar
  215. Suzuki Y et al (2010) Increased serum kynurenine/tryptophan ratio correlates with disease progression in lung cancer. Lung Cancer 67:361–365PubMedCrossRefGoogle Scholar
  216. Tabin CJ et al (1982) Mechanism of activation of a human oncogene. Nature 300:143–149PubMedCrossRefGoogle Scholar
  217. Takahiro H et al (2009) MicroRNA-133 regulates the expression of CPT-1b and GLUT4 by targeting SRF and KLF15 and is involved in metabolic control in cardiac myocytes. Biochem Biophys Res Commun 389:315–320CrossRefGoogle Scholar
  218. Tao T et al (2014) Loss of SNAIL inhibits cellular growth and metabolism through the miR-128-mediated RPS6KB1/HIF-1α/PKM2 signaling pathway in prostate cancer cells. Tumor Biol 35:8543–8550CrossRefGoogle Scholar
  219. Telang S, Yalcin A, Clem AL, Bucala R, Lane AN, Eaton JW, Chesney J (2006) Ras transformation requires metabolic control by 6-phosphofructo-2-kinase. Oncogene 25(55):7225–7234PubMedCrossRefGoogle Scholar
  220. Terunuma A et al (2014) MYC-driven accumulation of 2-hydroxyglutarate is associated with breast cancer prognosis. J Clin Investig 124:398–412PubMedCrossRefGoogle Scholar
  221. Valencia T et al (2014) Metabolic reprogramming of stromal fibroblasts through p62-mTORC1 signaling promotes inflammation and tumorigenesis. Cancer Cell 26:121–135PubMedPubMedCentralCrossRefGoogle Scholar
  222. Van Lith SA et al (2016) Identification of a novel inactivating mutation in Isocitrate Dehydrogenase 1 (IDH1-R314C) in a high grade astrocytoma. Sci Rep 6:30486–30494PubMedPubMedCentralCrossRefGoogle Scholar
  223. Vetter ML, Bishop JM (1988) Cellular ras activity and phospholipid metabolism. Cell 52:63–71CrossRefGoogle Scholar
  224. Vincent A, Van SI (2012) On the epigenetic origin of cancer stem cells. Biochim Biophys Acta 1826:83–88PubMedGoogle Scholar
  225. Walczak K et al (2011) Kynurenic acid synthesis and kynurenine aminotransferases expression in colon derived normal and cancer cells. Scand J Gastroenterol 46:903–912PubMedCrossRefGoogle Scholar
  226. Wang T et al (1976) Aerobic glycolysis during lymphocyte proliferation. Nature 261:702–705PubMedCrossRefGoogle Scholar
  227. Wang F, Travins J, Delabarre B, Penardlacronique V, Schalm S, Hansen E, Straley K, Kernytsky A, Liu W, Gliser C (2013a) Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiation. Science 340(6132):622–626CrossRefGoogle Scholar
  228. Wang Q, Tiffen J, Bailey CG, Lehman ML, Ritchie W, Fazli L, Metierre C, Feng Y, Li E, Gleave M (2013b) Targeting amino acid transport in metastatic castration-resistant prostate cancer: effects on cell cycle, cell growth, and tumor development. J Natl Cancer Inst 105(19):1463–1473PubMedCrossRefGoogle Scholar
  229. Wang HJ et al (2014) JMJD5 regulates PKM2 nuclear translocation and reprograms HIF-1α-mediated glucose metabolism. Proc Natl Acad Sci U S A 111:279–284PubMedCrossRefGoogle Scholar
  230. Wanka C et al (2012) Synthesis of cytochrome C oxidase 2: a p53-dependent metabolic regulator that promotes respiratory function and protects glioma and colon cancer cells from hypoxia-induced cell death. Oncogene 31:3764–3776PubMedCrossRefGoogle Scholar
  231. Warburg O (1956) On the origin of cancer cells. Science 123(3191):309–314PubMedCrossRefGoogle Scholar
  232. Warburg et al (1927) The metabolism of tumors in the body. J Gen Physiol 8:519–530PubMedPubMedCentralCrossRefGoogle Scholar
  233. Ward PS, Patel J, Wise DR, Abdelwahab O, Bennett BD, Coller HA, Cross JR, Fantin VR, Hedvat CV, Perl AE (2010) The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzymatic activity that converts α-ketoglutarate to 2-hydroxyglutarate. Cancer Cell 17(3):225–234PubMedPubMedCentralCrossRefGoogle Scholar
  234. Warner SL et al (2014) Activators of PKM2 in cancer metabolism. Future Med Chem 6:1167–1178PubMedCrossRefPubMedCentralGoogle Scholar
  235. Waterhouse C (2015) Lactate metabolism in patients with cancer. Cancer 33:66–71CrossRefGoogle Scholar
  236. Weinberg F et al (2010) Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity. Proc Natl Acad Sci U S A 107:8788–8793PubMedPubMedCentralCrossRefGoogle Scholar
  237. Wen CZ, Bing L (2014) Targeting metabolic enzyme with locked nucleic acids in non-small cell lung cancer. Cancer Res 74:1438–1438CrossRefGoogle Scholar
  238. Wigley WC, Nakashima RA (1992) Evidence for multiple genes coding for the isozymes of hexokinase in the highly glycolytic AS-30D rat hepatoma. FEBS Lett 300:153–156PubMedCrossRefGoogle Scholar
  239. Wong N et al (2015) PKM2 contributes to cancer metabolism. Cancer Lett 356:184–191PubMedCrossRefGoogle Scholar
  240. Woo CC et al (2018) Inhibiting glycine decarboxylase suppresses pyruvate-to-lactate metabolism in lung cancer cells. Front Oncol 8:1–12CrossRefGoogle Scholar
  241. Wu XZ (2008) Origin of cancer stem cells: the role of self-renewal and differentiation. Ann Surg Oncol 15:407–414PubMedCrossRefGoogle Scholar
  242. Xie X et al (2018) Diallyl disulfide inhibits breast cancer stem cell progression and glucose metabolism by targeting CD44/PKM2/AMPK signaling. Curr Cancer Drug Targets 18:592–599PubMedCrossRefGoogle Scholar
  243. Xu RH et al (2005) Inhibition of glycolysis in cancer cells: a novel strategy to overcome drug resistance associated with mitochondrial respiratory defect and hypoxia. Cancer Res 65:613–621PubMedGoogle Scholar
  244. Xu W, Yang H, Liu Y, Yang Y, Wang P et al (2011) Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. Cancer Cell 19(1):17–30PubMedPubMedCentralCrossRefGoogle Scholar
  245. Yang W et al (2011) Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation. Nature 480:118–122PubMedPubMedCentralCrossRefGoogle Scholar
  246. Yang W et al (2012a) PKM2 phosphorylates histone H3 and promotes gene transcription and tumorigenesis. Cell 150:685–696PubMedPubMedCentralCrossRefGoogle Scholar
  247. Yang W et al (2012b) ERK1/2-dependent phosphorylation and nuclear translocation of PKM2 promotes the Warburg effect. Nat Cell Biol 14:1295–1304PubMedPubMedCentralCrossRefGoogle Scholar
  248. Yang X et al (2015) A lentiviral sponge for miRNA-21 diminishes aerobic glycolysis in bladder cancer T24 cells via the PTEN/PI3K/AKT/mTOR axis. Tumor Biol 36:383–391CrossRefGoogle Scholar
  249. Yang G et al (2016) miR-100 antagonism triggers apoptosis by inhibiting ubiquitination-mediated p53 degradation. Oncogene 36:1023–1037PubMedCrossRefGoogle Scholar
  250. Yang L et al (2017) Glutaminolysis: a hallmark of cancer metabolism. Annu Rev Biomed Eng 19:163–167PubMedCrossRefGoogle Scholar
  251. Ye J et al (2012) Pyruvate kinase M2 promotes de novo serine synthesis to sustain mTORC1 activity and cell proliferation. Proc Natl Acad Sci U S A 109:6904–6909PubMedPubMedCentralCrossRefGoogle Scholar
  252. Yi L, Cao Y, Zhang W, Bergmeier S, Qian Y, Akbar H, Colvin R, Ding J, Tong L, Wu S (2012) A small-molecule inhibitor of glucose transporter 1 downregulates glycolysis, induces cell-cycle arrest, and inhibits cancer cell growth in vitro and in vivo. Mol Cancer Ther 11(8):1672–1682CrossRefGoogle Scholar
  253. Yi M et al (2013) Metabolic reprogramming in cancer: the art of balance. J Cent South Univ 38:1177–1187Google Scholar
  254. Young VR (1977) Energy metabolism and requirements in the cancer patient. Cancer Res 37:2336–2336PubMedPubMedCentralGoogle Scholar
  255. Zhang H et al (2007) HIF-1 inhibits mitochondrial biogenesis and cellular respiration in VHL-deficient renal cell carcinoma by repression of C-MYC activity. Cancer Cell 11:407–420PubMedCrossRefPubMedCentralGoogle Scholar
  256. Zhang WC et al (2012a) Glycinedecarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis. Cell 148:259–272PubMedCrossRefPubMedCentralGoogle Scholar
  257. Zhang G et al (2012b) Induced pluripotent stem cell consensus genes: implication for the risk of tumorigenesis and cancers in induced pluripotent stem cell therapy. Stem Cells Dev 21:955–964PubMedCrossRefPubMedCentralGoogle Scholar
  258. Zhang Y, Yang JM (2013) Altered energy metabolism in cancer: a unique opportunity for therapeutic intervention. Cancer Biol Ther 14(2):81–89PubMedPubMedCentralCrossRefGoogle Scholar
  259. Zhang F, Zhang Y, Zhao W, Deng K, Wang Z, Yang C, Ma L, Openkova MS, Hou Y, Li K (2017) Metabolomics for biomarker discovery in the diagnosis, prognosis, survival and recurrence of colorectal cancer: a systematic review. Oncotarget 8(21):35460–35472PubMedPubMedCentralGoogle Scholar
  260. Zheng J (2012) Energy metabolism of cancer: glycolysis versus oxidative phosphorylation. Oncol Lett 4:1151–1157PubMedPubMedCentralCrossRefGoogle Scholar
  261. Zhong W et al (2015) Oxysterol-binding protein-related protein 8 (ORP8) increases sensitivity of hepatocellular carcinoma cells to Fas-mediated apoptosis. J Biol Chem 290:8876–8887PubMedPubMedCentralCrossRefGoogle Scholar
  262. Zhou Y et al (2012) Golgi protein 73 versus alpha-fetoprotein as a biomarker for hepatocellular carcinoma: a diagnostic meta- analysis. BMC Cancer 12(1):17PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Bio-bank of Shenzhen Second People’s Hospital, Health Science CenterFirst Affiliated Hospital of Shenzhen UniversityShenzhenChina
  2. 2.College of Life SciencesZhejiang UniversityHangzhouChina

Personalised recommendations