Skip to main content
SpringerLink
Log in

Metabolic Regulation in Mitochondria and Drug Resistance

  • Chapter
  • First Online:
Book cover Mitochondrial DNA and Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1038))

Abstract

Mitochondria are generally considered as a powerhouse in a cell where the majority of the cellular ATP and metabolite productions occur. Metabolic rewiring and reprogramming may be initiated and regulated by mitochondrial enzymes. The hypothesis that cellular metabolic rewiring and reprogramming processes may occur as cellular microenvironment is disturbed, resulting in alteration of cell phenotype, such as cancer cells resistant to therapeutics seems to be now acceptable. Cancer metabolic reprogramming regulated by mitochondrial enzymes is now one of the hallmarks of cancer. This chapter provides an overview of cancer metabolism and summarizes progress made in mitochondria-mediated metabolic regulation in cancer drug resistance.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Taylor RW, Turnbull DM. Mitochondrial DNA mutations in human disease. Nat Rev Genet. 2005;6(5):389–402. [PubMed: 15861210]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Falk MJ, Sondheimer N. Mitochondrial genetic diseases. Curr Opin Pediatr. 2010;22(6):711–6. [PubMed: 21045694]

    Article  PubMed  PubMed Central  Google Scholar 

  3. Mullen AR, Wheaton WW, Jin ES, Chen PH, Sullivan LB, Cheng T, Yang Y, Linehan WM, Chandel NS, DeBerardinis RJ. Suppression of human tumor cell proliferation through mitochondrial targeting. FASEB J. 2002;16(9):1010–6. [PubMed: 12087062]

    Article  Google Scholar 

  4. Mullen AR, Wheaton WW, Jin ES, Chen PH, Sullivan LB, Cheng T, et al. Reductive carboxylation supports growth in tumour cells with defective mitochondria. Nature. 2011;481(7381):385–8. [PubMed: 22101431]

    PubMed  PubMed Central  Google Scholar 

  5. Tan AS, Baty JW, Dong LF, Bezawork-Geleta A, Endaya B, Goodwin J, Bajzikova M, Kovarova J, Peterka M, Yan B, Bezawork-Geleta A, Endaya B, Goodwin J, et al. Mitochondrial genome acquisition restores respiratory function and tumori-genic potential of cancer cells without mitochondrial DNA. Cell Metab. 2015;21(1):81–94. [PubMed: 25565207]

    Article  CAS  PubMed  Google Scholar 

  6. Bao L, Zhang Y, Wang J, Wang H, Dong N, Su X, Xu M, Wang X. Variations of chromosome 2 gene expressions among patients with lung cancer or non-cancer. Cell Biol Toxicol. 2016;32(5):419–35. [PMID: 27301951]

    Article  CAS  PubMed  Google Scholar 

  7. Possemato R, Marks KM, Shaul YD, Pacold ME, Kim D, Birsoy K, Sethumadhavan S, Woo HK, Jang HG, Jha AK, et al. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature. 2011;476(7360):346–50. [PubMed: 21760589]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Sellers K, Fox MP, Bousamra M 2nd, Slone SP, Higashi RM, Miller DM, Wang Y, Yan J, Yuneva MO, Deshpande R, et al. Pyruvate carboxylase is critical for non-small-cell lung cancer proliferation. J Clin Invest. 2015;125(2):687–98. [PubMed: 25607840]

    Article  PubMed  PubMed Central  Google Scholar 

  9. Shi L, Wang LY, Wang BB, Cretoiu SM, Wang Q, Wang XD, Chen CS. Regulatory mechanism of betacellulin in CXCL8 production from lung cancer cells through EGFR-PI3K pathway. J Transl Med. 2014;12:70. [PMID: 24629040]

    Article  PubMed  PubMed Central  Google Scholar 

  10. Pelicano H, Martin DS, RH X, Huang P. Glycolysis inhibition for anticancer treatment. Oncogene. 2006;25(34):4633–46. [PubMed: 16892078]

    Article  CAS  PubMed  Google Scholar 

  11. Levine AJ, Puzio-Kuter AM. The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes. Science. 2010;330(6009):1340–4. [PubMed: 21127244]

    Article  CAS  PubMed  Google Scholar 

  12. Bonuccelli G, Tsirigos A, Whitaker-Menezes D, Pavlides S, Pestell RG, Chiavarina B, Frank PG, Flomenberg N, Howell A, Martinez-Outschoorn UE, et al. Ketones and lactate “fuel” tumor growth and metastasis: evidence that epithelial cancer cells use oxidative mitochondrial metabolism. Cell Cycle. 2010;9(17):3506–14. [PubMed: 20818174]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Xu RH, Pelicano H, Zhou Y, Carew JS, Feng L, Bhalla KN, Keating MJ, Huang P. Inhibition of glycolysis in cancer cells: a novel strategy to overcome drug resistance associated with mitochondrial respiratory defect and hypoxia. Cancer Res. 2005;65(2):613–21. [PubMed: 15695406]

    CAS  PubMed  Google Scholar 

  14. Thomas PD, Kahn M. Kat3 coactivators in somatic stem cells and cancer stem cells: biological roles, evolution, and pharmacologic manipulation. Cell Biol Toxicol. 2016;32(1):61–81. [PMID: 27008332]

    Article  CAS  PubMed  Google Scholar 

  15. DeBerardinis RJ, Chandel NS. Fundamentals of cancer metabolism. Sci Adv. 2016;2(5):e1600200. [PubMed: 27386546]

    Article  PubMed  PubMed Central  Google Scholar 

  16. Seo JB, Jung SR, Hille B, Koh DS, Extracellular ATP. protects pancreatic duct epithelial cells from alcohol-induced damage through P2Y1 receptor-cAMP signal pathway. Cell Biol Toxicol. 2016;32(3):229–47. [PMID: 27197531]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Hardie DG, Schaffer BE, Brunet A. AMPK: an energy-sensing pathway with multiple inputs and outputs. Trends Cell Biol. 2016;26(3):190–201. [PubMed: 26616193]

    Article  CAS  PubMed  Google Scholar 

  18. DeBerardinis RJ, Sayed N, Ditsworth D, Thompson CB. Brick by brick: metabolism and tumor cell growth. Curr Opin Genet Dev. 2008;18:54–61. [PubMed: 18387799]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Cairns RA, Harris IS, Mak TW. Regulation of cancer cell metabolism. Nat Rev Cancer. 2011;11:85–95. [PubMed: 21258394]

    Article  CAS  PubMed  Google Scholar 

  20. Warburg O, Posener K, Negelein E, Über den Stoffwechsel d. Karzinomzellen. Biochem Z. 1924;152:309–44.

    CAS  Google Scholar 

  21. Warburg O. On the origin of cancer cells. Science (New York, NY). 1956;123:309–14. [PubMed: 13298683]

    Article  CAS  Google Scholar 

  22. Semenza GL, Artemov D, Bedi A, Bhujwalla Z, Chiles K, Feldser D, Laughner E, Ravi R, Simons J, Taghavi P, et al. ‘The metabolism of tumours’: 70 years later. Novartis Found Symp. 2001;240:251–60. discussion 260- 254. [PubMed: 11727934]

    Article  CAS  PubMed  Google Scholar 

  23. Gogvadze V, Zhivotovsky B, Orrenius S. The Warburg effect and mitochondrial stability in cancer cells. Mol Asp Med. 2010;31:60–74. [PubMed: 19995572]

    Article  CAS  Google Scholar 

  24. Kroemer G, Pouyssegur J. Tumor cell metabolism: cancer’s Achilles’ heel. Cancer Cell. 2008;13:472–82. [PubMed: 18538731]

    Article  CAS  PubMed  Google Scholar 

  25. Salway JG. Metabolism at a glance. Oxford: Blackwell Science; 2000.

    Google Scholar 

  26. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science (New York, NY). 2009;324:1029–33. [PubMed: 19460998]

    Article  CAS  Google Scholar 

  27. Som P, Atkins HL, Bandoypadhyay D, Fowler JS, MacGregor RR, Matsui K, Oster ZH, Sacker DF, Shiue CY, Turner H, et al. A fluorinated glucose analog, 2-fluoro-2-deoxy-D-glucose (F- 18): nontoxic tracer for rapid tumor detection. J Nucl Med. 1980;21:670–5. [PubMed: 7391842]

    CAS  PubMed  Google Scholar 

  28. Courtnay R, Ngo DC, Malik N, Ververis K, Tortorella SM, Karagiannis TC. Cancer metabolism and the Warburg effect: the role of HIF-1 and PI3K. Mol Biol Rep. 2015;42:841–51. [PubMed: 25689954]

    Article  CAS  PubMed  Google Scholar 

  29. Bayley JP, Devilee P. The Warburg effect in 2012. Curr Opin Oncol. 2012;24:62–7. [PubMed: 22123234]

    Article  CAS  PubMed  Google Scholar 

  30. Yeung SJ, Pan J, Lee MH. Roles of p53, MYC and HIF- 1 in regulating glycolysis – the seventh hallmark of cancer. Cell Mol Life Sci. 2008;65:3981–99. [PubMed: 18766298]

    Article  CAS  PubMed  Google Scholar 

  31. Li J, Zhu S, Tong J, Hao H, Yang J, Liu Z, Wang Y. Suppression of lactate dehydrogenase a compromises tumor progression by downregulation of the Warburg effect in glioblastoma. Neuroreport. 2016;27:110–5. [PubMed: 26694942]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Liberti MV, Locasale JW. The Warburg effect: how does it benefit cancer cells? Trends Biochem Sci. 2016;41:211–8. [PubMed: 26778478]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Yamamoto T, Seino Y, Fukumoto H, Koh G, Yano H, Inagaki N, Yamada Y, Inoue K, Manabe T, Imura H. Over-expression of facilitative glucose transporter genes in human cancer. Biochem Biophys Res Commun. 1990;170:223–30. [PubMed: 2372287]

    Article  CAS  PubMed  Google Scholar 

  34. Altenberg B, Greulich KO. Genes of glycolysis are ubiquitously overexpressed in 24 cancer classes. Genomics. 2004;84:1014–20. [PubMed: 15533718]

    Article  CAS  PubMed  Google Scholar 

  35. Levine AJ, Puzio-Kuter AM. The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes. Science (New York, NY). 2010;330:1340–4. [PubMed: 21127244]

    Article  CAS  Google Scholar 

  36. Cerella C, Dicato M, Diederich M. Modulatory roles of glycolytic enzymes in cell death. Biochem Pharmacol. 2014;92:22–30. [PubMed: 25034412]

    Article  CAS  PubMed  Google Scholar 

  37. Lippai M, Szatmári Z. Autophagy-from molecular mechanisms to clinical relevance. Cell Biol Toxicol. 2017;33(2):145–68. [PMID: 27957648]

    Article  CAS  PubMed  Google Scholar 

  38. Pastorino JG, Shulga N, Hoek JB. Mitochondrial binding of hexokinase II inhibits Bax-induced cytochrome c release and apoptosis. J Biol Chem. 2002;277:7610–8. [PubMed: 11751859]

    Article  CAS  PubMed  Google Scholar 

  39. Patra KC, Hay N. The pentose phosphate pathway and cancer. Trends Biochem Sci. 2014;39:347–54. [PubMed: 25037503]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Boros LG, Puigjaner J, Cascante M, Lee WN, Brandes JL, Bassilian S, Yusuf FI, Williams RD, Muscarella P, Melvin WS, et al. Oxythiamine and dehydroepiandrosterone inhibit the nonoxidative synthesis of ribose and tumor cell proliferation. Cancer Res. 1997;57:4242–8. [PubMed: 9331084]

    CAS  PubMed  Google Scholar 

  41. Tudzarova S, Colombo SL, Stoeber K, Carcamo S, Williams GH, Moncada S. Two ubiquitin ligases, APC/C-Cdh1 and SKP1-CUL1-F (SCF)-beta-TrCP, sequentially regulate glycolysis during the cell cycle. Proc Natl Acad Sci U S A. 2011;108:5278–83. [PubMed: 21402913]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Santos CR, Schulze A. Lipid metabolism in cancer. FEBS J. 2012;279:2610–23. [PubMed: 22621751]

    Article  CAS  PubMed  Google Scholar 

  43. Porstmann T, Griffiths B, Chung YL, Delpuech O, Griffiths JR, Downward J, Schulze A. PKB/Akt induces transcription of enzymes involved in cholesterol and fatty acid biosynthesis via activation of SREBP. Oncogene. 2005;24:6465–81. [PubMed: 16007182]

    Article  CAS  PubMed  Google Scholar 

  44. Yuan HX, Xiong Y, Guan KL. Nutrient sensing, metabolism, and cell growth control. Mol Cell. 2013;49:379–87. [PubMed: 23395268]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Tsun ZY, Possemato R. Amino acid management in cancer. Semin Cell Dev Biol. 2015;43:22–32. [PubMed: 26277542]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. P G, Tchernyshyov I, Chang TC, Lee YS, Kita K, Ochi T, Zeller KI, De Marzo AM, Van Eyk JE, Mendell JT, et al. c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature. 2009;458:762–5. [PubMed: 19219026]

    Article  Google Scholar 

  47. Kim J, Lee JH, Iyer VR. Global identification of Myc target genes reveals its direct role in mitochondrial biogenesis and its E-box usage in vivo. PLoS One. 2008;3:e1798. [PubMed: 18335064]

    Article  PubMed  PubMed Central  Google Scholar 

  48. Zhu M, Wang N, Tsao SW, Yuen MF, Feng Y, Wan TS, Man K. Up-regulation of microRNAs, miR21 and miR23a in human liver cancer cells treated with Coptidis rhizoma aqueous extract. Exp Ther Med. 2011;2:27–32. [PubMed: 22977465]

    Article  PubMed  Google Scholar 

  49. Nicklin P, Bergman P, Zhang B, Triantafellow E, Wang H, Nyfeler B, Yang H, Hild M, Kung C, Wilson C, Myer VE, MacKeigan JP, Porter JA, et al. Bidirectional transport of amino acids regulates mTOR and autophagy. Cell. 2009;136:521–34. [PubMed: 19203585]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Locasale JW. Serine, glycine and one-carbon units: cancer metabolism in full circle. Nat Rev Cancer. 2013;13:572–83. [PubMed: 23822983]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. di Salvo ML, Contestabile R, Paiardini A, Maras B. Glycine consumption and mitochondrial serine hydroxymethyltransferase in cancer cells: the heme connection. Med Hypotheses. 2013;80:633–6. [PubMed: 23474074]

    Article  PubMed  Google Scholar 

  52. Phang JM, Liu W, Hancock CN, Fischer JW. Proline metabolism and cancer: emerging links to glutamine and collagen. Curr Opin Clin Nutr Metab Care. 2015;18:71–7. [PubMed: 25474014]

    Article  CAS  PubMed  Google Scholar 

  53. Liu W, Phang JM. Proline dehydrogenase (oxidase) in cancer. Biofactors. 2012;38:398–406. [PubMed: 22886911]

    Article  CAS  PubMed  Google Scholar 

  54. Daye D, Wellen KE. Metabolic reprogramming in cancer: unraveling the role of glutamine in tumorigenesis. Semin Cell Dev Biol. 2012;23:362–9. [PubMed: 22349059]

    Article  CAS  PubMed  Google Scholar 

  55. Wise DR, Thompson CB. Glutamine addiction: a new therapeutic target in cancer. Trends Biochem Sci. 2010;35:427–33. [PubMed: 20570523]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. MO Y, Fan TW, Allen TD, Higashi RM, Ferraris DV, Tsukamoto T, Matés JM, Alonso FJ, Wang C, Seo Y, et al. The metabolic profile of tumors depends on both the responsible genetic lesion and tissue type. Cell Metab. 2012;15:157–70. [PubMed: 22326218]

    Article  Google Scholar 

  57. Iacobazzi V, Infantino V. Citrate—new functions for an old metabolite. Biol Chem. 2014;395:387–99. [PubMed: 24445237]

    Article  CAS  PubMed  Google Scholar 

  58. Boulahbel H, Duran RV, Gottlieb E. Prolyl hydroxylases as regulators of cell metabolism. Biochem Soc Trans. 2009;37:291–4. [PubMed: 19143649]

    Article  CAS  PubMed  Google Scholar 

  59. DeBerardinis RJ, Mancuso A, Daikhin E, Nissim I, Yudkoff M, Wehrli S, Thompson CB. Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc Natl Acad Sci U S A. 2007;104:19345–50. [PubMed: 18032601]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. XL Z, Guppy M. Cancer metabolism: facts, fantasy, and fiction. Biochem Biophys Res Commun. 2004;313:459–65. [PubMed: 14697210]

    Article  Google Scholar 

  61. Yang C, Sudderth J, Dang T, Bachoo RM, McDonald JG, DeBerardinis RJ. Glioblastoma cells require glutamate dehydrogenase to survive impairments of glucose metabolism or Akt signaling. Cancer Res. 2009;69:7986–93. [PubMed: 19826036]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Metallo CM, Gameiro PA, Bell EL, Mattaini KR, Yang J, Hiller K, Jewell CM, Johnson ZR, Irvine DJ, Guarente L, et al. Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia. Nature. 2012;481:380–4. [PubMed: 22101433]

    CAS  Google Scholar 

  63. Wallace DC. Mitochondria and cancer. Nat Rev Cancer. 2012;12:685–98. [PubMed: 23001348]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Acin-Perez R, Enriquez JA. The function of the respiratory supercomplexes: the plasticity model. Biochim Biophys Acta. 2014;1837:444–50. [PubMed: 24368156]

    Article  CAS  PubMed  Google Scholar 

  65. Xu W, Yang H, Liu Y, Yang Y, Wang P, Kim SH, Ito S, Yang C, Wang P, Xiao MT, et al. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases. Cancer Cell. 2011;19:17–30. [PubMed: 21251613]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Zhao S, Lin Y, Xu W, Jiang W, Zha Z, Wang P, Yu W, Li Z, Gong L, Peng Y, et al. Glioma-derived mutations in IDH1 dominantly inhibit IDH1 catalytic activity and induce HIF-1alpha. Science (New York, NY). 2009;324:261–5. [PubMed: 19359588]

    Article  CAS  Google Scholar 

  67. Losman JA, Kaelin WG Jr. What a difference a hydroxyl makes: mutant IDH, (R)-2-hydroxyglutarate, and cancer. Genes Dev. 2013;27:836–52. [PubMed: 23630074]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Rahman M, Hasan MR. Cancer metabolism and drug resistance. Metabolites. 2015;5:571–600. [PubMed: 26437434]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Anderson M, Marayati R, Moffitt R, Yeh JJ. Hexokinase 2 promotes tumor growth and metastasis by regulating lactate production in pancreatic cancer. Oncotarget. 2016;2:3762–3. [PubMed: 27259263]

    Google Scholar 

  70. Colell A, Ricci JE, Tait S, Milasta S, Maurer U, Bouchier-Hayes L, Fitzgerald P, Guio-Carrion A, Waterhouse NJ, Li CW, et al. GAPDH and autophagy preserve survival after apoptotic cytochrome c release in the absence of caspase activation. Cell. 2007;129:983–97. [PubMed: 17540177]

    Article  CAS  PubMed  Google Scholar 

  71. Lee DC, Sohn HA, Park ZY, Oh S, Kang YK, Lee KM, Kang M, Jang YJ, Yang SJ, Hong YK, et al. Article a lactate-induced response to hypoxia article alactate-Induced response to hypoxia. Cell. 2015;161:595–609. [PubMed: 25892225]

    Article  CAS  PubMed  Google Scholar 

  72. Zhou M, Zhao Y, Ding Y, Liu H, Liu Z, Fodstad O, Riker AI, Kamarajugadda S, Lu J, Owen LB, et al. Warburg effect in chemosensitivity: targeting lactate dehydrogenase–A re-sensitizes Taxol-resistant cancer cells to Taxol. Mol Cancer. 2010;9:1–12. [PubMed: 20144215]

    Google Scholar 

  73. Nakano Y, Tanno S, Koizumi K, Nishikawa T, Nakamura K, Minoguchi M, Izawa T, Mizukami Y, et al. Gemcitabine chemo resistance and molecular markers associated with gemcitabine transport and metabolism in human pancreatic cancer cells. Br J Cancer. 2007;96:457–63. [PubMed: 17224927]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Targeting cellular metabolism to improve cancer therapeutics. Cell Death Dis. 2012;71:4585–97.

    Google Scholar 

  75. Wang JB, Erickson JW, Fuji R, Ramachandran S, Gao P, Dinavahi R, Wilson KF, Ambrosio AL, Dias SM, Dang CV, et al. Targeting mitochondrial glutaminase activity inhibits oncogenic transformation. Cancer Cell. 2011;18:207–19. [PubMed: 20832749]

    Article  CAS  Google Scholar 

  76. Greijer AE, van der Wall E. The role of hypoxia inducible factor 1 (HIF-1) in hypoxia induced apoptosis. J Clin Pathol. 2004;57:1009–14. [PubMed: 15452150]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. He G, Jiang Y, Zhang B, Wu G. The effect of HIF-1 on glucose metabolism, growth and apoptosis of pancreatic cancerous cells. Asia Pac J Clin Nutr. 2014;23:174–80. [PubMed: 24561986]

    CAS  PubMed  Google Scholar 

  78. Golias T, Papandreou I, Sun R, Kumar B, Brown NV, Swanson BJ, Pai R, Jaitin D, Le QT, Teknos TN, et al. Hypoxic repression of pyruvate dehydrogenase activity is necessary for metabolic reprogramming and growth of model tumours. Sci Rep. 2016;6:311–21. [PubMed: 27498883]

    Article  Google Scholar 

  79. Haas M, Heinemann V, Kullmann F, Laubender RP, Klose C, Bruns CJ, Holdenrieder S, Modest DP, Schulz C, Boeck S. Prognostic value of CA 19-9, CEA, CRP, LDH and bilirubin levels in locally advanced and metastatic pancreatic cancer: results from a multicenter, pooled analysis of patients receiving palliative chemotherapy. J Cancer Res Clin Oncol. 2013;139:681–9. [PubMed: 23315099]

    Article  CAS  PubMed  Google Scholar 

  80. Fantin VR, St-Pierre J, Leder P. Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer Cell. 2006;9:425–34. [PubMed: 16766262]

    Article  CAS  PubMed  Google Scholar 

  81. Faivre S, Kroemer G, Raymond E. Current development of mTOR inhibitors as anticancer agents. Nature. 2006;5:671–88. [PubMed: 16883305]

    Article  CAS  Google Scholar 

  82. Dowling RJ, Topisirovic I, Alain T, Bidinosti M, Fonseca BD, Petroulakis E, Wang X, Larsson O, Selvaraj A, Liu Y, et al. mTORC1-mediated cell proliferation, but not cell growth, controlled by the 4E-BPs. Science. 2010;328:1172–6. [PubMed: 20508131]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Thomas GV, Tran C, Mellinghoff IK, Welsbie DS, Chan E, Fueger B, Czernin J, Sawyers CL. Hypoxia-inducible factor determines sensitivity to inhibitors of mTOR in kidney cancer. Nat Med. 2006;12:122–7. [PubMed: 16341243]

    Article  CAS  PubMed  Google Scholar 

  84. Iriana S, Ahmed S, Gong J, Annamalai AA, Tuli R, Hendifar AE. Targeting mTOR in pancreatic ductal adenocarcinoma. Front Oncol. 2016;6:99. [PubMed: 27200288]

    Article  PubMed  PubMed Central  Google Scholar 

  85. Wang X. New biomarkers and therapeutics can be discovered during COPD-lung cancer transition. Cell Biol Toxicol. 2016;32(5):359–61. [PMID: 27405768]

    Article  PubMed  Google Scholar 

  86. Gu J, Wang X. New future of cell biology and toxicology: thinking deeper. Cell Biol Toxicol. 2016;32(1):1–3. [PMID: 26874518]

    Article  PubMed  Google Scholar 

  87. Wang X. CBT profiles of cabozantinib approved for advanced renal cell carcinomas. Cell Biol Toxicol. 2016;32(4):259–61. [PMID: 27383755]

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The work was supported by the Dalian University of Technology Distinguished Professor Grant (Gary Guishan Xiao), the National Natural Science Foundation of China (81770846, 81642006, 81272430), Agi Hirshberg international pancreatic disease center funds (H2015PC01), talent introduction funds of Dalian University of Technology (852004), and major research projects of Dalian University of Technology (DUT17ZD308).

Author information

Authors and Affiliations

  1. School of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian, China

    Yue Pan, Min Cao, Jianzhou Liu, Qing Yang, Xiaoyu Miao & Gary Guishan Xiao

  2. Agi Hirshberg UCLA Center for Pancreas Diseases, University of California, Los Angeles, CA, USA

    Vay Liang W. Go & Gary Guishan Xiao

  3. Harbor University of California Los Angeles Medical Center, Torrance, CA, USA

    Paul W. N. Lee & Gary Guishan Xiao

  4. Functional Genomics and Proteomics Laboratories, Creighton University Medical Center, Omaha, NE, USA

    Gary Guishan Xiao

Authors
  1. Yue Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Min Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jianzhou Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qing Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiaoyu Miao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Vay Liang W. Go
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Paul W. N. Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Gary Guishan Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gary Guishan Xiao .

Editor information

Editors and Affiliations

  1. Liaoning Province Key Laboratory of Cancer Metabolomics, Jinzhou Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China

    Hongzhi Sun

  2. Zhongshan Hospital Institute of Clinical Science, Fudan University, Shanghai Medical College, Shanghai, China

    Xiangdong Wang

Rights and permissions

Reprints and permissions

Copyright information

© 2017 The Editor(s) (if applicable) and The Author(s) 2018

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Pan, Y. et al. (2017). Metabolic Regulation in Mitochondria and Drug Resistance. In: Sun, H., Wang, X. (eds) Mitochondrial DNA and Diseases. Advances in Experimental Medicine and Biology, vol 1038. Springer, Singapore. https://doi.org/10.1007/978-981-10-6674-0_11

Download citation

Publish with us

Policies and ethics

Search

Navigation