Login Register Cart 0
Generic placeholder image

Current Drug Discovery Technologies

Editor-in-Chief

ISSN (Print): 1570-1638
ISSN (Online): 1875-6220

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Cancer Cell Metabolism Featuring Nrf2

Author(s): Payal Chatterjee*, Mukesh Yadav, Namrata Chauhan, Ying Huang and Yun Luo

Volume 17, Issue 3, 2020

Page: [263 - 271] Pages: 9

DOI: 10.2174/1570163815666180911092443

Price: $65

Abstract

Although the major role of Nrf2 has long been established as a transcription factor for providing cellular protection against oxidative stress, multiple pieces of research and reviews now claim exactly the opposite. The dilemma - “to activate or inhibit” the protein requires an immediate answer, which evidently links cellular metabolism to the causes and purpose of cancer. Profusely growing cancerous cells have prolific energy requirements, which can only be fulfilled by modulating cellular metabolism. This review highlights the cause and effect of Nrf2 modulation in cancer that in turn channelize cellular metabolism, thereby fulfilling the energy requirements of cancer cells. The present work also highlights the purpose of genetic mutations in Nrf2, in relation to cellular metabolism in cancer cells, thus pointing out a newer approach where parallel mutations may be the key factor to decide whether to activate or inhibit Nrf2.

Keywords: Nrf2, keap1, Reactive Oxygenation Species [ROS], cancer, oxidative stress, glycolysis, glutathione, Tricarboxylic Acid Cycle [TCA], de novo lipogenesis.

Graphical Abstract

[1]
Moi P, Chan K, Asunis I, Cao A, Kan YW. Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region. Proc Natl Acad Sci USA 1994; 91(21): 9926-30.
[http://dx.doi.org/10.1073/pnas.91.21.9926] [PMID: 7937919]
[2]
Itoh K, Chiba T, Takahashi S, et al. An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem Biophys Res Commun 1997; 236(2): 313-22.
[http://dx.doi.org/10.1006/bbrc.1997.6943] [PMID: 9240432]
[3]
Kalthoff S, Ehmer U, Freiberg N, Manns MP, Strassburg CP. Interaction between oxidative stress sensor Nrf2 and xenobiotic-activated aryl hydrocarbon receptor in the regulation of the human phase II detoxifying UDP-glucuronosyltransferase 1A10. J Biol Chem 2010; 285(9): 5993-6002.
[http://dx.doi.org/10.1074/jbc.M109.075770] [PMID: 20053997]
[4]
Lee J-M, Calkins MJ, Chan K, Kan YW, Johnson JA. Identification of the NF-E2-related factor-2-dependent genes conferring protection against oxidative stress in primary cortical astrocytes using oligonucleotide microarray analysis. J Biol Chem 2003; 278(14): 12029-38.
[http://dx.doi.org/10.1074/jbc.M211558200] [PMID: 12556532]
[5]
Morito N, Yoh K, Itoh K, et al. Nrf2 regulates the sensitivity of death receptor signals by affecting intracellular glutathione levels. Oncogene 2003; 22(58): 9275-81.
[http://dx.doi.org/10.1038/sj.onc.1207024] [PMID: 14681686]
[6]
Zhang DD, Lo SC, Cross JV, Templeton DJ, Hannink M. Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex. Mol Cell Biol 2004; 24(24): 10941-53.
[http://dx.doi.org/10.1128/MCB.24.24.10941-10953.2004] [PMID: 15572695]
[7]
Zhang DD. Mechanistic studies of the Nrf2-Keap1 signaling pathway. Drug Metab Rev 2006; 38(4): 769-89.
[http://dx.doi.org/10.1080/03602530600971974] [PMID: 17145701]
[8]
Sykiotis GP, Habeos IG, Samuelson AV, Bohmann D. The role of the antioxidant and longevity-promoting Nrf2 pathway in metabolic regulation. Curr Opin Clin Nutr Metab Care 2011; 14(1): 41-8.
[http://dx.doi.org/10.1097/MCO.0b013e32834136f2] [PMID: 21102319]
[9]
Suh JH, Shenvi SV, Dixon BM, et al. Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. Proc Natl Acad Sci USA 2004; 101(10): 3381-6.
[http://dx.doi.org/10.1073/pnas.0400282101] [PMID: 14985508]
[10]
Kappos L, Gold R, Miller DH, et al. Effect of BG-12 on contrast-enhanced lesions in patients with relapsing--remitting multiple sclerosis: subgroup analyses from the phase 2b study. Mult Scler 2012; 18(3): 314-21.
[http://dx.doi.org/10.1177/1352458511421054] [PMID: 21878455]
[11]
González-Reyes S, Guzmán-Beltrán S, Medina-Campos ON, Pedraza-Chaverri J. Curcumin pretreatment induces Nrf2 and an antioxidant response and prevents hemin-induced toxicity in primary cultures of cerebellar granule neurons of rats. Oxid Med Cell Longev 2013; 2013801418
[http://dx.doi.org/10.1155/2013/801418] [PMID: 24454990]
[12]
Liu Z, Dou W, Zheng Y, et al. Curcumin upregulates Nrf2 nuclear translocation and protects rat hepatic stellate cells against oxidative stress. Mol Med Rep 2016; 13(2): 1717-24.
[http://dx.doi.org/10.3892/mmr.2015.4690] [PMID: 26676408]
[13]
Lu C, Xu W, Zhang F, Shao J, Zheng S. Nrf2 Knockdown Disrupts the Protective Effect of Curcumin on Alcohol-Induced Hepatocyte Necroptosis. Mol Pharm 2016; 13(12): 4043-53.
[http://dx.doi.org/10.1021/acs.molpharmaceut.6b00562] [PMID: 27764939]
[14]
Mostafavi-Pour Z, Ramezani F, Keshavarzi F, Samadi N. The role of quercetin and vitamin C in Nrf2-dependent oxidative stress production in breast cancer cells. Oncol Lett 2017; 13(3): 1965-73.
[http://dx.doi.org/10.3892/ol.2017.5619] [PMID: 28454351]
[15]
Bajpai VK, Alam MB, Quan KT, et al. Antioxidant efficacy and the upregulation of Nrf2-mediated HO-1 expression by (+)-lariciresinol, a lignan isolated from Rubia philippinensis, through the activation of p38. Sci Rep 2017; 7: 46035.
[http://dx.doi.org/10.1038/srep46035] [PMID: 28378774]
[16]
Iida K, Itoh K, Kumagai Y, et al. Nrf2 is essential for the chemopreventive efficacy of oltipraz against urinary bladder carcinogenesis. Cancer Res 2004; 64(18): 6424-31.
[http://dx.doi.org/10.1158/0008-5472.CAN-04-1906] [PMID: 15374950]
[17]
Ramos-Gomez M, Kwak M-K, Dolan PM, et al. Sensitivity to carcinogenesis is increased and chemoprotective efficacy of enzyme inducers is lost in nrf2 transcription factor-deficient mice. Proc Natl Acad Sci USA 2001; 98(6): 3410-5.
[http://dx.doi.org/10.1073/pnas.051618798] [PMID: 11248092]
[18]
DeNicola GM, Karreth FA, Humpton TJ, et al. Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis. Nature 2011; 475(7354): 106-9.
[http://dx.doi.org/10.1038/nature10189] [PMID: 21734707]
[19]
Ohta T, Iijima K, Miyamoto M, et al. Loss of Keap1 function activates Nrf2 and provides advantages for lung cancer cell growth. Cancer Res 2008; 68(5): 1303-9.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-5003] [PMID: 18316592]
[20]
Wang X-J, Sun Z, Villeneuve NF, et al. Nrf2 enhances resistance of cancer cells to chemotherapeutic drugs, the dark side of Nrf2. Carcinogenesis 2008; 29(6): 1235-43.
[http://dx.doi.org/10.1093/carcin/bgn095] [PMID: 18413364]
[21]
Gonzalez-Donquiles C, Alonso-Molero J, Fernandez-Villa T, Vilorio-Marqués L, Molina AJ, Martín V. The NRF2 transcription factor plays a dual role in colorectal cancer: A systematic review. PLoS One 2017; 12(5)e0177549
[http://dx.doi.org/10.1371/journal.pone.0177549] [PMID: 28542357]
[22]
Fan Z, Wirth AK, Chen D, et al. Nrf2-Keap1 pathway promotes cell proliferation and diminishes ferroptosis. Oncogenesis 2017; 6(8)e371
[http://dx.doi.org/10.1038/oncsis.2017.65] [PMID: 28805788]
[23]
Menegon S, Columbano A, Giordano S. The Dual Roles of NRF2 in Cancer. Trends Mol Med 2016; 22(7): 578-93.
[http://dx.doi.org/10.1016/j.molmed.2016.05.002] [PMID: 27263465]
[24]
Moon EJ, Giaccia A. Dual roles of NRF2 in tumor prevention and progression: possible implications in cancer treatment. Free Radic Biol Med 2015; 79: 292-9.
[http://dx.doi.org/10.1016/j.freeradbiomed.2014.11.009] [PMID: 25458917]
[25]
Milkovic L, Zarkovic N, Saso L. Controversy about pharmacological modulation of Nrf2 for cancer therapy. Redox Biol 2017; 12: 727-32.
[http://dx.doi.org/10.1016/j.redox.2017.04.013] [PMID: 28411557]
[26]
Rojo de la Vega M, Chapman E, Zhang DD. NRF2 and the Hallmarks of Cancer. Cancer Cell 2018; 34(1): 21-43.
[http://dx.doi.org/10.1016/j.ccell.2018.03.022] [PMID: 29731393]
[27]
Pandey P, Singh AK, Singh M, Tewari M, Shukla HS, Gambhir IS. The see-saw of Keap1-Nrf2 pathway in cancer. Crit Rev Oncol Hematol 2017; 116: 89-98.
[http://dx.doi.org/10.1016/j.critrevonc.2017.02.006] [PMID: 28693803]
[28]
Warburg O, Wind F, Negelein E. The metabolism of tumors in the body. J Gen Physiol 1927; 8(6): 519-30.
[http://dx.doi.org/10.1085/jgp.8.6.519] [PMID: 19872213]
[29]
Heiss EH, Schachner D, Zimmermann K, Dirsch VM. Glucose availability is a decisive factor for Nrf2-mediated gene expression. Redox Biol 2013; 1(1): 359-65.
[http://dx.doi.org/10.1016/j.redox.2013.06.001] [PMID: 24024172]
[30]
Mitsuishi Y, Taguchi K, Kawatani Y, 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] [PMID: 22789539]
[31]
Holmström KM, Baird L, Zhang Y, et al. Nrf2 impacts cellular bioenergetics by controlling substrate availability for mitochondrial respiration. Biol Open 2013; 2(8): 761-70.
[http://dx.doi.org/10.1242/bio.20134853] [PMID: 23951401]
[32]
Kowalik MA, Guzzo G, Morandi A, et al. Metabolic reprogramming identifies the most aggressive lesions at early phases of hepatic carcinogenesis. Oncotarget 2016; 7(22): 32375-93.
[http://dx.doi.org/10.18632/oncotarget.8632] [PMID: 27070090]
[33]
J.M. CSPL. Citric Acid Cycle Methods in Enzymology 13. Boston: Academic Press 1969.
[34]
Weitzman P, Ed. Krebs citric acid cycle: Half a century and still turning.
[35]
Rich P. The molecular machinery of Keilin’s respiratory chain. Portland Press Limited 2003.
[36]
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(6): 425-34.
[http://dx.doi.org/10.1016/j.ccr.2006.04.023] [PMID: 16766262]
[37]
Moreno-Sánchez R, Rodríguez-Enríquez S, Marín-Hernández A, Saavedra E. Energy metabolism in tumor cells. FEBS J 2007; 274(6): 1393-418.
[http://dx.doi.org/10.1111/j.1742-4658.2007.05686.x] [PMID: 17302740]
[38]
Wise DR, Ward PS, Shay JE, et al. Hypoxia promotes isocitrate dehydrogenase-dependent carboxylation of α-ketoglutarate to citrate to support cell growth and viability. Proc Natl Acad Sci USA 2011; 108(49): 19611-6.
[http://dx.doi.org/10.1073/pnas.1117773108] [PMID: 22106302]
[39]
Metallo CM, Gameiro PA, Bell EL, et al. Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia. Nature 2011; 481(7381): 380-4.
[http://dx.doi.org/10.1038/nature10602] [PMID: 22101433]
[40]
Mullen AR, Wheaton WW, Jin ES, et al. Reductive carboxylation supports growth in tumour cells with defective mitochondria. Nature 2011; 481(7381): 385-8.
[http://dx.doi.org/10.1038/nature10642] [PMID: 22101431]
[41]
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] [PMID: 16892081]
[42]
Parsons DW, Jones S, Zhang X, et al. An integrated genomic analysis of human glioblastoma multiforme. Science 2008; 321(5897): 1807-12.
[http://dx.doi.org/10.1126/science.1164382] [PMID: 18772396]
[43]
Ooi A, Wong J-C, Petillo 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] [PMID: 22014576]
[44]
Adam J, Hatipoglu E, O’Flaherty L, 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] [PMID: 22014577]
[45]
Sullivan LB, Martinez-Garcia E, Nguyen H, et al. The proto-oncometabolite fumarate binds glutathione to amplify ROS-dependent signaling. Mol Cell 2013; 51(2): 236-48.
[http://dx.doi.org/10.1016/j.molcel.2013.05.003] [PMID: 23747014]
[46]
Dang L, White DW, Gross S, et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 2010; 465(7300): 966.
[http://dx.doi.org/10.1038/nature09132] [PMID: 20559394]
[47]
Ward PS, Patel J, Wise DR, et al. The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. Cancer Cell 2010; 17(3): 225-34.
[http://dx.doi.org/10.1016/j.ccr.2010.01.020] [PMID: 20171147]
[48]
Dringen R, Pfeiffer B, Hamprecht B. Synthesis of the antioxidant glutathione in neurons: supply by astrocytes of CysGly as precursor for neuronal glutathione. J Neurosci 1999; 19(2): 562-9.
[http://dx.doi.org/10.1523/JNEUROSCI.19-02-00562.1999] [PMID: 9880576]
[49]
Griffith OW, Mulcahy RT. The enzymes of glutathione synthesis: gamma-glutamylcysteine synthetase Adv Enzymol Relat Areas Mol Biol 1999; 73 209-267, xii.[xii.].
[http://dx.doi.org/10.1002/9780470123195.ch7] [PMID: 10218110]
[50]
Kensler TW, Wakabayashi N, Biswal S. Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu Rev Pharmacol Toxicol 2007; 47: 89-116.
[http://dx.doi.org/10.1146/annurev.pharmtox.46.120604.141046] [PMID: 16968214]
[51]
Vafa O, Wade M, Kern S, et al. c-Myc can induce DNA damage, increase reactive oxygen species, and mitigate p53 function: a mechanism for oncogene-induced genetic instability. Mol Cell 2002; 9(5): 1031-44.
[http://dx.doi.org/10.1016/S1097-2765(02)00520-8] [PMID: 12049739]
[52]
Markovic J, Borrás C, Ortega A, Sastre J, Viña J, Pallardó FV. Glutathione is recruited into the nucleus in early phases of cell proliferation. J Biol Chem 2007; 282(28): 20416-24.
[http://dx.doi.org/10.1074/jbc.M609582200] [PMID: 17452333]
[53]
Rahman I. Regulation of nuclear factor-kappa B, activator protein-1, and glutathione levels by tumor necrosis factor-alpha and dexamethasone in alveolar epithelial cells. Biochem Pharmacol 2000; 60(8): 1041-9.
[http://dx.doi.org/10.1016/S0006-2952(00)00392-0] [PMID: 11007940]
[54]
Reddy NM, Kleeberger SR, Cho HY, et al. Deficiency in Nrf2-GSH signaling impairs type II cell growth and enhances sensitivity to oxidants. Am J Respir Cell Mol Biol 2007; 37(1): 3-8.
[http://dx.doi.org/10.1165/rcmb.2007-0004RC] [PMID: 17413030]
[55]
Armstrong JS, Steinauer KK, Hornung B, et al. Role of glutathione depletion and reactive oxygen species generation in apoptotic signaling in a human B lymphoma cell line. Cell Death Differ 2002; 9(3): 252-63.
[http://dx.doi.org/10.1038/sj.cdd.4400959] [PMID: 11859408]
[56]
Reddy NM, Kleeberger SR, Bream JH, et al. Genetic disruption of the Nrf2 compromises cell-cycle progression by impairing GSH-induced redox signaling. Oncogene 2008; 27(44): 5821-32.
[http://dx.doi.org/10.1038/onc.2008.188] [PMID: 18542053]
[57]
Carretero J, Obrador E, Anasagasti MJ, Martin JJ, Vidal-Vanaclocha F, Estrela JM. Growth-associated changes in glutathione content correlate with liver metastatic activity of B16 melanoma cells. Clin Exp Metastasis 1999; 17(7): 567-74.
[http://dx.doi.org/10.1023/A:1006725226078] [PMID: 10845555]
[58]
Huang ZZ, Chen C, Zeng Z, et al. Mechanism and significance of increased glutathione level in human hepatocellular carcinoma and liver regeneration. FASEB J 2001; 15(1): 19-21.
[http://dx.doi.org/10.1096/fj.00-0445fje] [PMID: 11099488]
[59]
Trachootham D, Alexandre J, Huang P. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov 2009; 8(7): 579-91.
[http://dx.doi.org/10.1038/nrd2803] [PMID: 19478820]
[60]
Lien EC, Lyssiotis CA, Juvekar A, et al. Glutathione biosynthesis is a metabolic vulnerability in PI(3)K/Akt-driven breast cancer. Nat Cell Biol 2016; 18(5): 572-8.
[http://dx.doi.org/10.1038/ncb3341] [PMID: 27088857]
[61]
Furfaro AL, Piras S, Domenicotti C, et al. Role of Nrf2, HO-1 and GSH in Neuroblastoma Cell Resistance to Bortezomib. PLoS One 2016; 11(3)e0152465
[http://dx.doi.org/10.1371/journal.pone.0152465] [PMID: 27023064]
[62]
Roh JL, Jang H, Kim EH, Shin D. Targeting of the Glutathione, Thioredoxin, and Nrf2 Antioxidant Systems in Head and Neck Cancer Antioxidants & redox signaling 2017; 27(2): 106-4
[63]
Rocha CR, Kajitani GS, Quinet A, Fortunato RS, Menck CF. NRF2 and glutathione are key resistance mediators to temozolomide in glioma and melanoma cells. Oncotarget 2016; 7(30): 48081-92.
[http://dx.doi.org/10.18632/oncotarget.10129] [PMID: 27344172]
[64]
Brusselmans K, Timmermans L, Van de Sande T, et al. Squalene synthase, a determinant of Raft-associated cholesterol and modulator of cancer cell proliferation. J Biol Chem 2007; 282(26): 18777-85.
[http://dx.doi.org/10.1074/jbc.M611763200] [PMID: 17483544]
[65]
Kuemmerle NB, Rysman E, Lombardo PS, et al. Lipoprotein lipase links dietary fat to solid tumor cell proliferation. Mol Cancer Ther 2011; 10(3): 427-36.
[http://dx.doi.org/10.1158/1535-7163.MCT-10-0802] [PMID: 21282354]
[66]
Menendez JA, Lupu R. Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat Rev Cancer 2007; 7(10): 763-77.
[http://dx.doi.org/10.1038/nrc2222] [PMID: 17882277]
[67]
Sebti SM. Protein farnesylation: implications for normal physiology, malignant transformation, and cancer therapy. Cancer Cell 2005; 7(4): 297-300.
[http://dx.doi.org/10.1016/j.ccr.2005.04.005] [PMID: 15837619]
[68]
Zaidi N, Lupien L, Kuemmerle NB, Kinlaw WB, Swinnen JV, Smans K. Lipogenesis and lipolysis: the pathways exploited by the cancer cells to acquire fatty acids. Prog Lipid Res 2013; 52(4): 585-9.
[http://dx.doi.org/10.1016/j.plipres.2013.08.005] [PMID: 24001676]
[69]
Ray U, Roy SS. Aberrant lipid metabolism in cancer cells - the role of oncolipid-activated signaling. FEBS J 2018; 285(3): 432-43.
[http://dx.doi.org/10.1111/febs.14281] [PMID: 28971574]
[70]
Nelson DLC. MM Lehninger Principles of Biochemistry. Worth Publishers 2000.
[71]
Medes G, Thomas A, Weinhouse S. Metabolism of neoplastic tissue. IV. A study of lipid synthesis in neoplastic tissue slices in vitro. Cancer Res 1953; 13(1): 27-9.
[PMID: 13032945]
[72]
Abramson HN. The lipogenesis pathway as a cancer target. J Med Chem 2011; 54(16): 5615-38.
[http://dx.doi.org/10.1021/jm2005805] [PMID: 21726077]
[73]
Igal RA. Stearoyl-CoA desaturase-1: a novel key player in the mechanisms of cell proliferation, programmed cell death and transformation to cancer. Carcinogenesis 2010; 31(9): 1509-15.
[http://dx.doi.org/10.1093/carcin/bgq131] [PMID: 20595235]
[74]
Santos CR, Schulze A. Lipid metabolism in cancer. FEBS J 2012; 279(15): 2610-23.
[http://dx.doi.org/10.1111/j.1742-4658.2012.08644.x] [PMID: 22621751]
[75]
Swinnen JV, Brusselmans K, Verhoeven G. Increased lipogenesis in cancer cells: new players, novel targets. Curr Opin Clin Nutr Metab Care 2006; 9(4): 358-65.
[http://dx.doi.org/10.1097/01.mco.0000232894.28674.30] [PMID: 16778563]
[76]
Murai T. The role of lipid rafts in cancer cell adhesion and migration. Int J Cell Biol 2012; 2012763283
[http://dx.doi.org/10.1155/2012/763283] [PMID: 22253629]
[77]
Simons K, Gerl MJ. Revitalizing membrane rafts: new tools and insights. Nat Rev Mol Cell Biol 2010; 11(10): 688-99.
[http://dx.doi.org/10.1038/nrm2977] [PMID: 20861879]
[78]
Rysman E, Brusselmans K, Scheys K, et al. De novo lipogenesis protects cancer cells from free radicals and chemotherapeutics by promoting membrane lipid saturation. Cancer Res 2010; 70(20): 8117-26.
[http://dx.doi.org/10.1158/0008-5472.CAN-09-3871] [PMID: 20876798]
[79]
Pang S, Lynn DA, Lo JY, Paek J, Curran SP. SKN-1 and Nrf2 couples proline catabolism with lipid metabolism during nutrient deprivation. Nat Commun 2014; 5: 5048.
[http://dx.doi.org/10.1038/ncomms6048] [PMID: 25284427]
[80]
Fritz V, Fajas L. Metabolism and proliferation share common regulatory pathways in cancer cells. Oncogene 2010; 29(31): 4369-77.
[http://dx.doi.org/10.1038/onc.2010.182] [PMID: 20514019]
[81]
Michalek RD, Rathmell JC. The metabolic life and times of a T-cell. Immunol Rev 2010; 236: 190-202.
[http://dx.doi.org/10.1111/j.1600-065X.2010.00911.x] [PMID: 20636818]
[82]
Shibata T, Ohta T, Tong KI, et al. Cancer related mutations in NRF2 impair its recognition by Keap1-Cul3 E3 ligase and promote malignancy. Proc Natl Acad Sci USA 2008; 105(36): 13568-73.
[http://dx.doi.org/10.1073/pnas.0806268105] [PMID: 18757741]
[83]
Shibata T, Kokubu A, Gotoh M, Ojima H, Ohta T, Yamamoto M, et al. Genetic alteration of Keap1 confers constitutive Nrf2 activation and resistance to chemotherapy in gallbladder cancer 2008; 135(4): 1358-68,. 68 e1-4.
[http://dx.doi.org/10.1053/j.gastro.2008.06.082]
[84]
Yoo NJ, Kim HR, Kim YR, An CH, Lee SH. Somatic mutations of the KEAP1 gene in common solid cancers. Histopathology 2012; 60(6): 943-52.
[http://dx.doi.org/10.1111/j.1365-2559.2012.04178.x] [PMID: 22348534]
[85]
Shibata T, Kokubu A, Saito S, et al. NRF2 mutation confers malignant potential and resistance to chemoradiation therapy in advanced esophageal squamous cancer. Neoplasia 2011; 13(9): 864-73.
[http://dx.doi.org/10.1593/neo.11750] [PMID: 21969819]
[86]
Goldstein LD, Lee J, Gnad F, et al. Recurrent Loss of NFE2L2 Exon 2 Is a Mechanism for Nrf2 Pathway Activation in Human Cancers. Cell Rep 2016; 16(10): 2605-17.
[http://dx.doi.org/10.1016/j.celrep.2016.08.010] [PMID: 27568559]
[87]
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144(5): 646-74.
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID: 21376230]

Rights & Permissions Print Cite
Article Metrics
25
© 2024 Bentham Science Publishers | Privacy Policy