Metabolic Imbalance Associated Mitophagy in Tumor Cells: Genesis and Implications

Authors

  • Madhuri Chaurasia Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, Delhi 110054, India
  • Shashank Misra Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, Delhi 110054, India
  • Anant N. Bhatt Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, Delhi 110054, India
  • Asmita Das Department of Biotechnology, Delhi Technological University, Delhi 110042, India
  • Bilikere Dwarakanath Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, Delhi 110054, India
  • Kulbhushan Sharma Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, Delhi 110054, India

DOI:

https://doi.org/10.6000/1929-2279.2015.04.02.8

Keywords:

Warburg, PARKIN, Oxidative stress, Metabolic Reprogramming, Calcium.

Abstract

 Emerging knowledge supports the notion that metabolic reprogramming facilitates the progression of many cancers and in some it could be initiated by mutations in genes related to mitochondrial function. While dysfunctional mitochondria plays a pivotal role in driving metabolic reprogramming, mitophagy that recycles damaged mitochondria by selective and organized degradation appears to be vital for sustaining carcinogenesis. Although the potential of targeting mitophagy as a therapeutic strategy has still remained elusive, poor prognosis and therapeutic resistance of highly glycolytic tumors suggest that inhibitors of mitophagy could be potential adjuvant in radio- and chemotherapy of tumors. We briefly review the current status of knowledge on the interrelationship between mitophagy and metabolic reprogramming during carcinogenesis and examine mitophagy as a potential target for developing anticancer therapeutics and adjuvant.

References

Valente EM, Abou-Sleiman PM, Caputo V, Muqit MM, Harvey K, Gispert S, et al. Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science 2004; 304(5674): 1158-60. http://dx.doi.org/10.1126/science.1096284

Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, et al. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 1998; 392(6676): 605-8. http://dx.doi.org/10.1038/33416

Warburg O. On the origin of cancer cells. Science 1956: 123(3191): 309-14. http://dx.doi.org/10.1126/science.123.3191.309

Pavlides S, Vera I, Gandara R, Sneddon S, Pestell RG, Mercier I, et al. Warburg meets autophagy: cancer-associated fibroblasts accelerate tumor growth and metastasis via oxidative stress, mitophagy, and aerobic glycolysis. Antioxid Redox Signal 2012; 16(11): 1264-84. http://dx.doi.org/10.1089/ars.2011.4243

Hughson LR, Poon VI, Spowart JE, Lum JJ. Implications of therapy-induced selective autophagy on tumor metabolism and survival. Int J Cell Biol 2012: 872091. http://dx.doi.org/10.1155/2012/872091

Warburg O: The metabolism of tumors. Constable and Co., London 1930.

Gogvadze V, Zhivotovsky B, Orrenius S. The Warburg effect and mitochondrial stability in cancer cells. Molecular Aspects of Medicine 2010; 31(1): 60-74. http://dx.doi.org/10.1016/j.mam.2009.12.004

Deberardinis RJ, Sayed N, Ditsworth D, Thompson CB. Brick by brick: metabolism and tumor cell growth. Current Opinion in Genetics & Development 2008; 18(1): 5461. http://dx.doi.org/10.1016/j.gde.2008.02.003

DeBerardinis RJ, Cheng T. Q's next: the diverse functions of glutamine in metabolism, cell biology and cancer. Oncogene 2010; 29(3): 313-24. http://dx.doi.org/10.1038/onc.2009.358

Hsu PP, Sabatini DM. Cancer cell metabolism: Warburg and beyond. Cell 2008; 134(5): 703-7. http://dx.doi.org/10.1016/j.cell.2008.08.021

Jones RG, Thompson CB. Tumor suppressors and cell metabolism: a recipe for cancer growth. Genes Dev 2009; 23(5): 537-48. http://dx.doi.org/10.1101/gad.1756509

Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 2009; 324(5930): 1029-33. http://dx.doi.org/10.1126/science.1160809

Tong X, Zhao F, Thompson CB. The molecular determinants of de novo nucleotide biosynthesis in cancer cells. Current Opinion in Genetics & Development 2009; 19(1): 32-7. http://dx.doi.org/10.1016/j.gde.2009.01.002

Locasale JW, Grassian AR, Melman T, Lyssiotis CA, Mattaini KR, Bass AJ, et al. Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis. Nature Genetics 2011; 43(9): 869-74. http://dx.doi.org/10.1038/ng.890

Anastasiou D, Poulogiannis G, Asara JM, Boxer MB, Jiang JK, Shen M, et al. Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses. Science 2011; 334(6060): 1278-83. http://dx.doi.org/10.1126/science.1211485

Hamanaka RB, Chandel NS. Cell biology. Warburg effect and redox balance. Science 2011; 334(6060): 1219-20. http://dx.doi.org/10.1126/science.1215637

Weinhouse S. The Warburg hypothesis fifty years later. Z Krebsforsch Klin Onkol Cancer Res Clin Oncol 1976; 87(2): 115-26. http://dx.doi.org/10.1007/BF00284370

Darzynkiewicz Z, Staiano-Coico L, Melamed MR. Increased mitochondrial uptake of rhodamine 123 during lymphocyte stimulation. Proc Natl Acad Sci U S A 1981; 78(4): 2383-7. http://dx.doi.org/10.1073/pnas.78.4.2383

Hedeskov CJ. Early effects of phytohaemagglutinin on glucose metabolism of normal human lymphocytes. The Biochemical Journal 1968; 110(2): 373-80.

Wang T, Marquardt C, Foker J. Aerobic glycolysis during lymphocyte proliferation. Nature 1976; 261(5562): 702-5. http://dx.doi.org/10.1038/261702a0

Lunt SY, Vander Heiden MG. Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Annual Review of Cell and Developmental Biology 2011; 27: 441-64. http://dx.doi.org/10.1146/annurev-cellbio-092910-154237

Munyon WH, Merchant DJ. The relation between glucose utilization, lactic acid production and utilization and the growth cycle of L strain fibroblasts. Experimental Cell Research 1959; 17(3): 490-8. http://dx.doi.org/10.1016/0014-4827(59)90069-2

Fogal V, Richardson AD, Karmali PP, Scheffler IE, Smith JW, Ruoslahti E. Mitochondrial p32 protein is a critical regulator of tumor metabolism via maintenance of oxidative phosphory-lation. Molecular and Cellular Biology 2010; 30(6): 1303-18. http://dx.doi.org/10.1128/MCB.01101-09

Guo JY, Chen HY, Mathew R, Fan J, Strohecker AM, Karsli-Uzunbas G, et al. Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis. Genes Dev 2011; 25(5): 460-70. http://dx.doi.org/10.1101/gad.2016311

Exner N, Lutz AK, Haass C, Winklhofer KF. Mitochondrial dysfunction in Parkinson's disease: molecular mechanisms and pathophysiological consequences. EMBO J 2012; 31(14): 3038-62. http://dx.doi.org/10.1038/emboj.2012.170

Winklhofer KF, Haass C. Mitochondrial dysfunction in Parkinson's disease. Biochim Biophys Acta 2010; 1802(1): 29-44. http://dx.doi.org/10.1016/j.bbadis.2009.08.013

Schapira AH. Mitochondrial disease. Lancet 2006; 368(9529): 70-82. http://dx.doi.org/10.1016/S0140-6736(06)68970-8

Pieczenik SR, Neustadt J. Mitochondrial dysfunction and molecular pathways of disease. Experimental and Molecular Pathology 2007; 83(1): 84-92. http://dx.doi.org/10.1016/j.yexmp.2006.09.008

Boland ML, Chourasia AH, Macleod KF. Mitochondrial dysfunction in cancer. Front Oncol 2013; 3: 292. http://dx.doi.org/10.3389/fonc.2013.00292

King A, Selak MA, Gottlieb E. Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer. Oncogene 2006; 25(34): 4675-82. http://dx.doi.org/10.1038/sj.onc.1209594

Canter JA, Kallianpur AR, Parl FF, Millikan RC. Mitochondrial DNA G10398A polymorphism and invasive breast cancer in African-American women. Cancer Res 2005; 65(17): 8028-33.

Petros JA, Baumann AK, Ruiz-Pesini E, Amin MB, Sun CQ, Hall J, et al. mtDNA mutations increase tumorigenicity in pro-state cancer. Proc Natl Acad Sci U S A 2005; 102(3): 719-24. http://dx.doi.org/10.1073/pnas.0408894102

Tomlinson IP, Alam NA, Rowan AJ, Barclay E, Jaeger EE, Kelsell D, et al. Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nature Genetics 2002; 30(4): 406-10. http://dx.doi.org/10.1038/ng849

Baysal BE, Ferrell RE, Willett-Brozick JE, Lawrence EC, Myssiorek D, Bosch A, et al. Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science 2000; 287(5454): 848-51. http://dx.doi.org/10.1126/science.287.5454.848

Sabharwal SS, Schumacker PT. Mitochondrial ROS in cancer: initiators, amplifiers or an Achilles' heel? Nature Reviews Cancer 2014; 14(11): 709-21. http://dx.doi.org/10.1038/nrc3803

Kroemer G. Mitochondria in cancer. Oncogene 2006; 25(34): 4630-2. http://dx.doi.org/10.1038/sj.onc.1209589

Koppenol WH, Bounds PL, Dang CV. Otto Warburg's contributions to current concepts of cancer metabolism. Nature Reviews Cancer 2011; 11(5): 325-37. http://dx.doi.org/10.1038/nrc3038

Wallace DC. Mitochondria and cancer. Nature Reviews Cancer 2012; 12(10): 685-98. http://dx.doi.org/10.1038/nrc3365

Kurelac I, Romeo G, Gasparre G. Mitochondrial metabolism and cancer. Mitochondrion 2011; 11(4): 635-7. http://dx.doi.org/10.1016/j.mito.2011.03.012

Bardella C, Pollard PJ, Tomlinson I. SDH mutations in cancer. Biochim Biophys Acta 2011; 1807(11): 1432-43. http://dx.doi.org/10.1016/j.bbabio.2011.07.003

Wallace DC, Fan W. Energetics, epigenetics, mitochondrial genetics. Mitochondrion 2010; 10(1): 12-31. http://dx.doi.org/10.1016/j.mito.2009.09.006

Adam J, Hatipoglu E, O'Flaherty L, Ternette N, Sahgal N, Lockstone H, et al. Renal cyst formation in Fh1-deficient mice is independent of the Hif/Phd pathway: roles for fumarate in KEAP1 succination and Nrf2 signaling. Cancer Cell 2011; 20(4): 524-37. http://dx.doi.org/10.1016/j.ccr.2011.09.006

Ooi A, Wong JC, Petillo D, Roossien D, Perrier-Trudova V, Whitten D, et al. An antioxidant response phenotype shared between hereditary and sporadic type 2 papillary renal cell carcinoma. Cancer Cell 2011; 20(4): 511-23. http://dx.doi.org/10.1016/j.ccr.2011.08.024

Lee SR, Yang KS, Kwon J, Lee C, Jeong W, Rhee SG. Reversible inactivation of the tumor suppressor PTEN by H2O2. J Biol Chem 2002; 277(23): 20336-42. http://dx.doi.org/10.1074/jbc.M111899200

Buhrman G, Parker B, Sohn J, Rudolph J, Mattos C. Structural mechanism of oxidative regulation of the phosphatase Cdc25B via an intramolecular disulfide bond. Biochemistry 2005; 44(14): 5307-16. http://dx.doi.org/10.1021/bi047449f

Kamata H, Honda S, Maeda S, Chang L, Hirata H, Karin M. Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases. Cell 2005; 120(5): 649-61. http://dx.doi.org/10.1016/j.cell.2004.12.041

Chandel NS, McClintock DS, Feliciano CE, Wood TM, Melendez JA, Rodriguez AM, et al. Reactive oxygen species generated at mitochondrial complex III stabilize hypoxia-inducible factor-1alpha during hypoxia: a mechanism of O2 sensing. J Biol Chem 2000; 275(33): 25130-8. http://dx.doi.org/10.1074/jbc.M001914200

Kim JW, Tchernyshyov I, Semenza GL, Dang CV. HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metabolism 2006; 3(3): 177-85. http://dx.doi.org/10.1016/j.cmet.2006.02.002

Papandreou I, Cairns RA, Fontana L, Lim AL, Denko NC. HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metabolism 2006; 3(3): 187-97. http://dx.doi.org/10.1016/j.cmet.2006.01.012

Choksi S, Lin Y, Pobezinskaya Y, Chen L, Park C, Morgan M, et al. A HIF-1 target, ATIA, protects cells from apoptosis by modulating the mitochondrial thioredoxin, TRX2. Molecular Cell 2011; 42(5): 597-609. http://dx.doi.org/10.1016/j.molcel.2011.03.030

Hayes JD, McMahon M. NRF2 and KEAP1 mutations: permanent activation of an adaptive response in cancer. Trends in Biochemical Sciences 2009; 34(4): 176-88. http://dx.doi.org/10.1016/j.tibs.2008.12.008

Mitsuishi Y, Taguchi K, Kawatani Y, Shibata T, Nukiwa T, Aburatani H, et al. Nrf2 redirects glucose and glutamine into anabolic pathways in metabolic reprogramming. Cancer Cell 2012; 22(1): 66-79. http://dx.doi.org/10.1016/j.ccr.2012.05.016

Roberts DJ, Tan-Sah VP, Smith JM, Miyamoto S. Akt phosphorylates HK-II at Thr-473 and increases mitochondrial HK-II association to protect cardiomyocytes. J Biol Chem 2013; 288(33): 23798-806. http://dx.doi.org/10.1074/jbc.M113.482026

Zhang Y, Yang JM. Altered energy metabolism in cancer: a unique opportunity for therapeutic intervention. Cancer Biology & Therapy 2013; 14(2): 81-9. http://dx.doi.org/10.4161/cbt.22958

Chen X, Qian Y, Wu S. The Warburg effect: evolving interpretations of an established concept. Free Radical Biology & Medicine 2015; 79: 253-63. http://dx.doi.org/10.1016/j.freeradbiomed.2014.08.027

Verma A, Bhatt AN, Farooque A, Khanna S, Singh S, Dwarakanath BS. Calcium ionophore A23187 reveals calcium related cellular stress as "I-Bodies": an old actor in a new role. Cell Calcium 2011; 50(6): 510-22. http://dx.doi.org/10.1016/j.ceca.2011.08.007

Serhan C, Anderson P, Goodman E, Dunham P, Weissmann G. Phosphatidate and oxidized fatty acids are calcium ionophores. Studies employing arsenazo III in liposomes. J Biol Chem 1981; 256(6): 2736-41.

Griffiths EJ, Rutter GA. Mitochondrial calcium as a key regulator of mitochondrial ATP production in mammalian cells. Biochim Biophys Acta 2009; 1787(11): 1324-33. http://dx.doi.org/10.1016/j.bbabio.2009.01.019

Ristow M, Schmeisser K. Mitohormesis: Promoting Health and Lifespan by Increased Levels of Reactive Oxygen Species (ROS). Dose Response 2014; 12(2): 288-341. http://dx.doi.org/10.2203/dose-response.13-035.Ristow

Rimessi A, Bonora M, Marchi S, Patergnani S, Marobbio CM, Lasorsa FM, et al. Perturbed mitochondrial Ca2+ signals as causes or consequences of mitophagy induction. Autophagy 2013; 9(11): 1677-86. http://dx.doi.org/10.4161/auto.24795

Gogvadze V, Orrenius S, Zhivotovsky B. Mitochondria in cancer cells: what is so special about them? Trends Cell Biol 2008; 18(4): 165-73. http://dx.doi.org/10.1016/j.tcb.2008.01.006

McLelland GL, Soubannier V, Chen CX, McBride HM, Fon EA. Parkin and PINK1 function in a vesicular trafficking pathway regulating mitochondrial quality control. Embo J 2014; 33(4): 282-95. http://dx.doi.org/10.1002/embj.201385902

Aita VM, Liang XH, Murty VV, Pincus DL, Yu W, Cayanis E, et al. Cloning and genomic organization of beclin 1, a candidate tumor suppressor gene on chromosome 17q21. Genomics 1999; 59(1): 59-65. http://dx.doi.org/10.1006/geno.1999.5851

Kim I, Rodriguez-Enriquez S, Lemasters JJ. Selective degradation of mitochondria by mitophagy. Arch Biochem Biophys 2007; 462(2): 245-53. http://dx.doi.org/10.1016/j.abb.2007.03.034

Youle RJ, Narendra DP. Mechanisms of mitophagy. Nat Rev Mol Cell Biol 2011; 12(1): 9-14. http://dx.doi.org/10.1038/nrm3028

Twig G, Hyde B, Shirihai OS. Mitochondrial fusion, fission and autophagy as a quality control axis: the bioenergetic view. Biochim Biophys Acta 2008; 1777(9): 1092-7. http://dx.doi.org/10.1016/j.bbabio.2008.05.001

Ehses S, Raschke I, Mancuso G, Bernacchia A, Geimer S, Tondera D, et al. Regulation of OPA1 processing and mitochondrial fusion by m-AAA protease isoenzymes and OMA1. J Cell Biol 2009; 187(7): 1023-36. http://dx.doi.org/10.1083/jcb.200906084

Head B, Griparic L, Amiri M, Gandre-Babbe S, van der Bliek AM. Inducible proteolytic inactivation of OPA1 mediated by the OMA1 protease in mammalian cells. J Cell Biol 2009; 187(7): 959-66. http://dx.doi.org/10.1083/jcb.200906083

Twig G, Elorza A, Molina AJ, Mohamed H, Wikstrom JD, Walzer G, et al. Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. Embo J 2008; 27(2): 433-46. http://dx.doi.org/10.1038/sj.emboj.7601963

Graef M, Nunnari J. Mitochondria regulate autophagy by conserved signalling pathways. Embo J 2011; 30(11): 2101-14. http://dx.doi.org/10.1038/emboj.2011.104

Gomes LC, Di Benedetto G, Scorrano L. During autophagy mitochondria elongate, are spared from degradation and sustain cell viability. Nat Cell Biol 2011; 13(5): 589-98. http://dx.doi.org/10.1038/ncb2220

Rambold AS, Kostelecky B, Elia N, Lippincott-Schwartz J. Tubular network formation protects mitochondria from autophagosomal degradation during nutrient starvation. Proc Natl Acad Sci U S A 2011; 108(25): 10190-5. http://dx.doi.org/10.1073/pnas.1107402108

Liu L, Feng D, Chen G, Chen M, Zheng Q, Song P, et al. Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells. Nat Cell Biol 2012; 14(2): 177-85. http://dx.doi.org/10.1038/ncb2422

Zhang J, Ney PA. Role of BNIP3 and NIX in cell death, autophagy, and mitophagy. Cell Death Differ 2009; 16(7): 939-46. http://dx.doi.org/10.1038/cdd.2009.16

Saraste M. Oxidative phosphorylation at the fin de siecle. Science 1999; 283(5407): 1488-93. http://dx.doi.org/10.1126/science.283.5407.1488

Wallace DC. A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu Rev Genet 2005; 39: 359-407. http://dx.doi.org/10.1146/annurev.genet.39.110304.095751

Parsons MJ, Green DR. Mitochondria in cell death. Essays Biochem.2010; 47: 99-114. http://dx.doi.org/10.1042/bse0470099

Chen Y, Dorn GW, 2nd. PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria. Science 2013; 340(6131): 471-5. http://dx.doi.org/10.1126/science.1231031

Fu M, St-Pierre P, Shankar J, Wang PT, Joshi B, Nabi IR. Regulation of mitophagy by the Gp78 E3 ubiquitin ligase. Mol Biol Cell 2013; 24(8): 1153-62. http://dx.doi.org/10.1091/mbc.E12-08-0607

Kanki T, Wang K, Baba M, Bartholomew CR, Lynch-Day MA, Du Z, et al. A genomic screen for yeast mutants defective in selective mitochondria autophagy. Mol Biol Cell 2009; 20(22): 4730-8. http://dx.doi.org/10.1091/mbc.E09-03-0225

Welter E, Montino M, Reinhold R, Schlotterhose P, Krick R, Dudek J, et al. Uth1 is a mitochondrial inner membrane protein dispensable for post-log-phase and rapamycin-induced mitophagy. Febs J 2013; 280(20): 4970-82. http://dx.doi.org/10.1111/febs.12468

Deas E, Plun-Favreau H, Gandhi S, Desmond H, Kjaer S, Loh SH, et al. PINK1 cleavage at position A103 by the mitochondrial protease PARL. Hum Mol Genet 2011; 20(5): 867-79. http://dx.doi.org/10.1093/hmg/ddq526

Ivatt RM, Whitworth AJ. The many faces of mitophagy. EMBO Rep 2014; 15(1): 5-6. http://dx.doi.org/10.1002/embr.201338224

Matsuda N, Sato S, Shiba K, Okatsu K, Saisho K, Gautier CA, et al. PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy. J Cell Biol 2010; 189(2): 211-21. http://dx.doi.org/10.1083/jcb.200910140

Kongara S, Karantza V. The interplay between autophagy and ROS in tumorigenesis. Front Oncol 2012; 2: 171. http://dx.doi.org/10.3389/fonc.2012.00171

Fujiwara M, Marusawa H, Wang HQ, Iwai A, Ikeuchi K, Imai Y, et al. Parkin as a tumor suppressor gene for hepatocellular carcinoma. Oncogene 2008; 27(46): 6002-11. http://dx.doi.org/10.1038/onc.2008.199

Zhang C, Lin M, Wu R, Wang X, Yang B, Levine AJ, et al. Parkin, a p53 target gene, mediates the role of p53 in glucose metabolism and the Warburg effect. Proc Natl Acad Sci U S A 2011; 108(39): 16259-64. http://dx.doi.org/10.1073/pnas.1113884108

Geisler S, Holmstrom KM, Skujat D, Fiesel FC, Rothfuss OC, Kahle PJ, et al. PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat Cell Biol 2010; 12(2): 119-31. http://dx.doi.org/10.1038/ncb2012

Picchio MC, Martin ES, Cesari R, Calin GA, Yendamuri S, Kuroki T, et al. Alterations of the tumor suppressor gene Parkin in non-small cell lung cancer. Clin Cancer Res 2004; 10(8): 2720-4. http://dx.doi.org/10.1158/1078-0432.CCR-03-0086

Cesari R, Martin ES, Calin GA, Pentimalli F, Bichi R, McAdams H, et al. Parkin, a gene implicated in autosomal recessive juvenile parkinsonism, is a candidate tumor suppressor gene on chromosome 6q25-q27. Proc Natl Acad Sci U S A 2003; 100(10): 5956-61. http://dx.doi.org/10.1073/pnas.0931262100

Koop EA, van Laar T, van Wichen DF, de Weger RA, Wall E, van Diest PJ. Expression of BNIP3 in invasive breast cancer: correlations with the hypoxic response and clinicopathological features. BMC Cancer 2009; 9: 175. http://dx.doi.org/10.1186/1471-2407-9-175

Okami J, Simeone DM, Logsdon CD. Silencing of the hypoxia-inducible cell death protein BNIP3 in pancreatic cancer. Cancer Res 2004; 64(15): 5338-46. http://dx.doi.org/10.1158/0008-5472.CAN-04-0089

Sowter HM, Ferguson M, Pym C, Watson P, Fox SB, Han C, et al. Expression of the cell death genes BNip3 and NIX in ductal carcinoma in situ of the breast; correlation of BNip3 levels with necrosis and grade. J Pathol 2003; 201(4): 573-80. http://dx.doi.org/10.1002/path.1486

Tan EY, Campo L, Han C, Turley H, Pezzella F, Gatter KC, et al. BNIP3 as a progression marker in primary human breast cancer; opposing functions in in situ versus invasive cancer. Clin Cancer Res 2007; 13(2 Pt 1): 467-74. http://dx.doi.org/10.1158/1078-0432.CCR-06-1466

Abe T, Toyota M, Suzuki H, Murai M, Akino K, Ueno M, et al. Upregulation of BNIP3 by 5-aza-2'-deoxycytidine sensitizes pancreatic cancer cells to hypoxia-mediated cell death. J Gastroenterol 2005; 40(5): 504-10. http://dx.doi.org/10.1007/s00535-005-1576-1

Castro M, Grau L, Puerta P, Gimenez L, Venditti J, Quadrelli S, et al. Multiplexed methylation profiles of tumor suppressor genes and clinical outcome in lung cancer. J Transl Med 2010; 8: 86. http://dx.doi.org/10.1186/1479-5876-8-86

Murai M, Toyota M, Suzuki H, Satoh A, Sasaki Y, Akino K, et al. Aberrant methylation and silencing of the BNIP3 gene in colorectal and gastric cancer. Clin Cancer Res 2005; 11(3): 1021-7.

Guo JY, Karsli-Uzunbas G, Mathew R, Aisner SC, Kamphorst JJ, Strohecker AM, et al. Autophagy suppresses progression of K-ras-induced lung tumors to oncocytomas and maintains lipid homeostasis. Genes Dev 2013; 27(13): 1447-61. http://dx.doi.org/10.1101/gad.219642.113

Fujiwara M, Marusawa H, Wang HQ, Iwai A, Ikeuchi K, Imai Y, et al. Parkin as a tumor suppressor gene for hepatocellular carcinoma. Oncogene 2008; 27(46): 6002-11. http://dx.doi.org/10.1038/onc.2008.199

Lu H, Li G, Liu L, Feng L, Wang X, Jin H. Regulation and function of mitophagy in development and cancer. Autophagy 2013; 9(11): 1720-36. http://dx.doi.org/10.4161/auto.26550

Chatterjee A, Mambo E, Sidransky D. Mitochondrial DNA mutations in human cancer. Oncogene 2006; 25(34): 4663-74. http://dx.doi.org/10.1038/sj.onc.1209604

Rosenfeldt MT, O'Prey J, Morton JP, Nixon C, MacKay G, Mrowinska A, et al. p53 status determines the role of autophagy in pancreatic tumour development. Nature 2013; 504(7479): 296-300. http://dx.doi.org/10.1038/nature12865

Kim JH, Kim HY, Lee YK, Yoon YS, Xu WG, Yoon JK, et al. Involvement of mitophagy in oncogenic K-Ras-induced transformation: overcoming a cellular energy deficit from glucose deficiency. Autophagy 2011; 7(10): 1187-98. http://dx.doi.org/10.4161/auto.7.10.16643

Casey TM, Eneman J, Crocker A, White J, Tessitore J, Stanley M, et al. Cancer associated fibroblasts stimulated by transforming growth factor beta1 (TGF-beta 1) increase invasion rate of tumor cells: a population study. Breast Cancer Res Treat 2008; 110(1): 39-49. http://dx.doi.org/10.1007/s10549-007-9684-7

Desmouliere A, Geinoz A, Gabbiani F, Gabbiani G. Transforming growth factor-beta 1 induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts. J Cell Biol 1993; 122(1): 103-11. http://dx.doi.org/10.1083/jcb.122.1.103

Direkze NC, Hodivala-Dilke K, Jeffery R, Hunt T, Poulsom R, Oukrif D, et al. Bone marrow contribution to tumor-associated myofibroblasts and fibroblasts. Cancer Res 2004; 64(23): 8492-5. http://dx.doi.org/10.1158/0008-5472.CAN-04-1708

Kojima Y, Acar A, Eaton EN, Mellody KT, Scheel C, Ben-Porath I, et al. Autocrine TGF-beta and stromal cell-derived factor-1 (SDF-1) signaling drives the evolution of tumor-promoting mammary stromal myofibroblasts. Proc Natl Acad Sci U S A 2010; 107(46): 20009-14. http://dx.doi.org/10.1073/pnas.1013805107

Martinez-Outschoorn UE, Pavlides S, Whitaker-Menezes D, Daumer KM, Milliman JN, Chiavarina B, et al. Tumor cells induce the cancer associated fibroblast phenotype via caveolin-1 degradation: implications for breast cancer and DCIS therapy with autophagy inhibitors. Cell Cycle 2010; 9(12): 2423-33. http://dx.doi.org/10.4161/cc.9.12.12048

Mishra PJ, Mishra PJ, Humeniuk R, Medina DJ, Alexe G, Mesirov JP, et al. Carcinoma-associated fibroblast-like differentiation of human mesenchymal stem cells. Cancer Res 2008; 68(11): 4331-9. http://dx.doi.org/10.1158/0008-5472.CAN-08-0943

Orimo A, Gupta PB, Sgroi DC, Arenzana-Seisdedos F, Delaunay T, Naeem R, et al. Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell 2005; 121(3): 335-48. http://dx.doi.org/10.1016/j.cell.2005.02.034

Waghray M, Cui Z, Horowitz JC, Subramanian IM, Martinez FJ, Toews GB, et al. Hydrogen peroxide is a diffusible paracrine signal for the induction of epithelial cell death by activated myofibroblasts. Faseb J 2005; 19(7): 854-6. http://dx.doi.org/10.1096/fj.04-2882fje

Whitaker-Menezes D, Martinez-Outschoorn UE, Lin Z, Ertel A, Flomenberg N, Witkiewicz AK, et al. Evidence for a stromal-epithelial "lactate shuttle" in human tumors: MCT4 is a marker of oxidative stress in cancer-associated fibroblasts. Cell Cycle 2011; 10(11): 1772-83. http://dx.doi.org/10.4161/cc.10.11.15659

Pinheiro C, Longatto-Filho A, Scapulatempo C, Ferreira L, Martins S, Pellerin L, et al. Increased expression of monocarboxylate transporters 1, 2, and 4 in colorectal carcinomas. Virchows Arch 2008; 452(2): 139-46. http://dx.doi.org/10.1007/s00428-007-0558-5

Sharma K L, Tiwari M, Mishra K S. Mitochondrial Alteration: A Major Player in Carcinogenesis. Cell Biology 2015; 3(2-1): 8-16.

Mahmoud SM, Paish EC, Powe DG, Macmillan RD, Grainge MJ, Lee AH, et al. Tumor-infiltrating CD8+ lymphocytes predict clinical outcome in breast cancer. J Clin Oncol 2011; 29(15): 1949-55. http://dx.doi.org/10.1200/JCO.2010.30.5037

Lou Y, Liu C, Kim GJ, Liu YJ, Hwu P, Wang G. Plasmacytoid dendritic cells synergize with myeloid dendritic cells in the induction of antigen-specific antitumor immune responses. J Immunol 2007; 178(3): 1534-41. http://dx.doi.org/10.4049/jimmunol.178.3.1534

Kundu N, Ma X, Holt D, Goloubeva O, Ostrand-Rosenberg S, Fulton AM. Antagonism of the prostaglandin E receptor EP4 inhibits metastasis and enhances NK function. Breast Cancer Res Treat 2009; 117(2): 235-42. http://dx.doi.org/10.1007/s10549-008-0180-5

Moretta L, Pietra G, Montaldo E, Vacca P, Pende D, Falco M, et al. Human NK cells: from surface receptors to the therapy of leukemias and solid tumors. Front Immunol 2014; 5: 87. http://dx.doi.org/10.3389/fimmu.2014.00087

Otera H, Wang C, Cleland MM, Setoguchi K, Yokota S, Youle RJ, et al. Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cells. J Cell Biol 2010; 191(6): 1141-58. http://dx.doi.org/10.1083/jcb.201007152

Guido C, Whitaker-Menezes D, Lin Z, Pestell RG, Howell A, Zimmers TA, et al. Mitochondrial fission induces glycolytic reprogramming in cancer-associated myofibroblasts, driving stromal lactate production, and early tumor growth. Oncotarget 2010; 3(8): 798-810.

Kubli DA, Gustafsson AB. Mitochondria and mitophagy: the yin and yang of cell death control. Circ Res 2012; 111(9): 1208-21. http://dx.doi.org/10.1161/CIRCRESAHA.112.265819

Chourasia AH, Boland ML, Macleod KF. Mitophagy and cancer. Cancer Metab 2015; 3: 4. http://dx.doi.org/10.1186/s40170-015-0130-8

Dwaraknath BS. Cytotoxicity, radiosensitization and chemosensitization of tumor cells by 2-deoxy-D-glucose in vitro. J. Cancer Res Ther.2009; 5: S27-S31. http://dx.doi.org/10.4103/0973-1482.55137

Dwarakanath BS and Jain V. Targeting glucose metabolism with 2-deoxy-D-glucose for improving cancer therapy (Invited Editorial). Future Oncol 2009; 5: 581-585. http://dx.doi.org/10.2217/fon.09.44

Jain V: Modifications of radiation responses by 2-deoxy-D-glucose in normal and cancer cells. Ind J Nucl Med 1996; 11, 8-17

Dwarakanath BS, Zolzer F, Chandna S, Bauch T, Adhikari JS, Muller WU, Streffer C and Jain V: Heterogeneity in 2-deoxy-D-glucose induced modifications in energetic and radiation responses of human tumor cell lines. Int. J. Radiation Oncology Biology Phys 2001; 51, 1151-1161. http://dx.doi.org/10.1016/S0360-3016(01)01534-6

Mohanti BK, Rath GK, Anantha N et al.: Improving cancer radiotherapy with 2-deoxy-D-glucose: phase I/II clinical trials on human cerebral gliomas. Int. J. Radiat. Oncol. Biol. Phys 1996; 35: 103-11. http://dx.doi.org/10.1016/S0360-3016(96)85017-6

Gao P, Zhang H, Dinavahi R, Li F, Xiang Y, Raman V, et al. HIF-dependent antitumorigenic effect of antioxidants in vivo. Cancer Cell 2007; 12(3): 230-8. http://dx.doi.org/10.1016/j.ccr.2007.08.004

Ma Q, Cavallin LE, Yan B, Zhu S, Duran EM, Wang H, et al. Antitumorigenesis of antioxidants in a transgenic Rac1 model of Kaposi's sarcoma. Proc Natl Acad Sci U S A 2009; 106(21): 8683-8. http://dx.doi.org/10.1073/pnas.0812688106

Gargini R, Garcia-Escudero V, Izquierdo M. Therapy mediated by mitophagy abrogates tumor progression. Autophagy 2011; 7(5): 466-76. http://dx.doi.org/10.4161/auto.7.5.14731

Saddoughi SA, Ogretmen B. Diverse functions of ceramide in cancer cell death and proliferation. Advances in cancer research 2013; 117: 37-58. http://dx.doi.org/10.1016/B978-0-12-394274-6.00002-9

Narendra D, Tanaka A, Suen DF, Youle RJ. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol 2008; 183(5): 795-803. http://dx.doi.org/10.1083/jcb.200809125

Ligeret H, Barthelemy S, Bouchard Doulakas G, Carrupt PA, Tillement JP, Labidalle S, et al. Fluoride curcumin derivatives: new mitochondrial uncoupling agents. FEBS Lett 2004; 569(1-3): 37-42. http://dx.doi.org/10.1016/j.febslet.2004.05.032

Galluzzi L, Larochette N, Zamzami N, Kroemer G. Mitochondria as therapeutic targets for cancer chemotherapy. Oncogene 2006; 25(34): 4812-30. http://dx.doi.org/10.1038/sj.onc.1209598

Milane L, Duan Z, Amiji M. Therapeutic efficacy and safety of paclitaxel/lonidamine loaded EGFR-targeted nanoparticles for the treatment of multi-drug resistant cancer. PLoS One 2011; 6(9): e24075. http://dx.doi.org/10.1371/journal.pone.0024075

Floridi A, Bruno T, Miccadei S, Fanciulli M, Federico A, Paggi MG. Enhancement of doxorubicin content by the antitumor drug lonidamine in resistant Ehrlich ascites tumor cells through modulation of energy metabolism. Biochem Pharmacol 1998; 56(7): 841-9. http://dx.doi.org/10.1016/S0006-2952(98)00054-9

Wang X, Leung AW, Luo J, Xu C. TEM observation of ultrasound-induced mitophagy in nasopharyngeal carcinoma cells in the presence of curcumin. Experimental and therapeutic medicine 2012; 3(1): 146-8.

Pavlides S, Tsirigos A, Vera I, Flomenberg N, Frank PG, Casimiro MC, et al. Loss of stromal caveolin-1 leads to oxidative stress, mimics hypoxia and drives inflammation in the tumor microenvironment, conferring the "reverse Warburg effect": a transcriptional informatics analysis with validation. Cell Cycle 2010; 9(11): 2201-19. http://dx.doi.org/10.4161/cc.9.11.11848

Sotgia F, Martinez-Outschoorn UE, Pavlides S, Howell A, Pestell RG, Lisanti MP. Understanding the Warburg effect and the prognostic value of stromal caveolin-1 as a marker of a lethal tumor microenvironment. Breast Cancer Res 2011; 13(4): 213. http://dx.doi.org/10.1186/bcr2892

Witkiewicz AK, Whitaker-Menezes D, Dasgupta A, Philp NJ, Lin Z, Gandara R, et al. Using the "reverse Warburg effect" to identify high-risk breast cancer patients: stromal MCT4 predicts poor clinical outcome in triple-negative breast cancers. Cell Cycle 2012; 11(6): 1108-17. http://dx.doi.org/10.4161/cc.11.6.19530

Downloads

Published

2015-04-29

How to Cite

Madhuri Chaurasia, Shashank Misra, Anant N. Bhatt, Asmita Das, Bilikere Dwarakanath, & Kulbhushan Sharma. (2015). Metabolic Imbalance Associated Mitophagy in Tumor Cells: Genesis and Implications. Journal of Cancer Research Updates, 4(2),  95–107. https://doi.org/10.6000/1929-2279.2015.04.02.8