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Volume 52 Issue 1
Jan.  2021
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WANG Kui, MING Hui, ZUO Jing, et al. A Review of the Redox Regulation of Tumor Metabolism[J]. JOURNAL OF SICHUAN UNIVERSITY (MEDICAL SCIENCE EDITION), 2021, 52(1): 57-63. doi: 10.12182/20210160204
Citation: WANG Kui, MING Hui, ZUO Jing, et al. A Review of the Redox Regulation of Tumor Metabolism[J]. JOURNAL OF SICHUAN UNIVERSITY (MEDICAL SCIENCE EDITION), 2021, 52(1): 57-63. doi: 10.12182/20210160204

A Review of the Redox Regulation of Tumor Metabolism

doi: 10.12182/20210160204
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  • Corresponding author: E-mail: hcanhua@hotmail.com
  • Received Date: 2020-11-09
  • Rev Recd Date: 2020-12-29
  • Publish Date: 2021-01-20
  • Metabolic aberrance is one of the hallmarks of cancer. The metabolic patterns in cancer cells are well reprogrammed to provide building blocks and energy for their sustained growth. During tumor metabolic reprogramming, reactive oxygen species (ROS) are generated and the antioxidant systems are activated. High levels of ROS lead to oxidative damage and even cell death, whereas ROS at low levels act as second messenger to regulate many signaling pathways. Recently, with the revisiting of oxidative stress, it has been found that ROS can directly mediate the redox modifications of proteins, resulting in protein conformational and functional alterations. However, only a very small portion of metabolic enzymes, including glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and PKM2, etc., has been reported to undergo redox modifications. Whether other metabolic enzymes are regulated by redox modifications and thus exhibit critical functions remain largely unknown. Moreover, the specific spatio-temporal targeting of redox modifications of metabolic enzymes, as well as overcoming the existed redox and metabolic adaptation, are key points to be solved. Here, we will review the reported redox modification patterns of metabolic enzymes, the involved regulatory mechanisms and their roles in tumorigenesis and tumor progress. In addition, we will discuss the future therapeutic strategies targeting redox modifications of metabolic enzymes for tumor treatment.
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  • [1]
    WARBURG O, WIND F, NEGELEIN E. The metabolism of tumors in the body. J Gen Physiol,1927,8(6): 519–530. doi: 10.1085/jgp.8.6.519
    [2]
    VERNIERI C, CASOLA S, FOIANI M, et al. Targeting cancer metabolism: dietary and pharmacologic interventions. Cancer Discov,2016,6(12): 1315–1333. doi: 10.1158/2159-8290.CD-16-0615
    [3]
    WANG C, HE C, LU S, et al. Autophagy activated by silibinin contributes to glioma cell death via induction of oxidative stress-mediated BNIP3-dependent nuclear translocation of AIF. Cell Death Dis,2020,11(8): 1–16. doi: 10.1038/s41419-020-02866-3
    [4]
    HAUGRUD A B, ZHUANG Y, COPPOCK J D, et al. Dichloroacetate enhances apoptotic cell death via oxidative damage and attenuates lactate production in metformin-treated breast cancer cells. Breast Cancer Res Treat,2014,147(3): 539–550. doi: 10.1007/s10549-014-3128-y
    [5]
    BERGAGGIO E, RIGANTI C, GARAFFO G, et al. IDH2 inhibition enhances proteasome inhibitor responsiveness in hematological malignancies. Blood,2019,133(2): 156–167. doi: 10.1182/blood-2018-05-850826
    [6]
    XIANG Y, STINE Z E, XIA J, et al. Targeted inhibition of tumor-specific glutaminase diminishes cell-autonomous tumorigenesis. J Clin Invest,2015,125(6): 2293–2306. doi: 10.1172/JCI75836
    [7]
    YUAN L, SHENG X, CLARK L H, et al. Glutaminase inhibitor compound 968 inhibits cell proliferation and sensitizes paclitaxel in ovarian cancer. Am J Transl Res,2016,8(10): 4265–4277.
    [8]
    JONES C L, STEVENS B M, D'ALESSANDRO A, et al. Inhibition of amino acid metabolism selectively targets human leukemia stem cells. Cancer Cell,2018,34(5): 724–740. doi: 10.1016/j.ccell.2018.10.005
    [9]
    CHENG S, WANG G, WANG Y, et al. Fatty acid oxidation inhibitor etomoxir suppresses tumor progression and induces cell cycle arrest via PPARγ-mediated pathway in bladder cancer. Clin Sci,2019,133(15): 1745–1758. doi: 10.1042/CS20190587
    [10]
    LI L, JIANG Z, YAO Y, et al. (−)-Hydroxycitric acid regulates energy metabolism by activation of AMPK-PGC1α-NRF1 signal pathway in primary chicken hepatocytes. Life Sci, 2020, 254: 117785 [2020-04-20]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5648812/. doi: 10.1038/s41467-017-01106-1.
    [11]
    SOSA V, MOLIN T, SOMOZA R, et al. Oxidative stress and cancer: an overview. Ageing Res Rev,2013,12(1): 376–390. doi: 10.1016/j.arr.2012.10.004
    [12]
    SIES H, JONES D P. Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nat Rev Mol Cell Biol,2020,21(7): 363–383. doi: 10.1038/s41580-020-0230-3
    [13]
    WANG K, JIANG J, LEI Y, et al. Targeting metabolic–redox circuits for cancer therapy. Trends Biochem Sci,2019,44(5): 401–414. doi: 10.1016/j.tibs.2019.01.001
    [14]
    CLEMENTINO M, SHI X, ZHANG Z. Oxidative stress and metabolic reprogramming in Cr (Ⅵ) carcinogenesis. Curr Opin Toxicol,2018,8(1): 20–27. doi: 10.1016/j.cotox.2017.11.015
    [15]
    SONG I K, LEE J J, CHO J H, et al. Degradation of redox-sensitive proteins including peroxiredoxins and DJ-1 is promoted by oxidation-induced conformational changes and ubiquitination. Sci Rep,2016,6(1): 1–15. doi: 10.1038/s41598-016-0001-8
    [16]
    SMITH K A, WAYPA G B, SCHUMACKER P T. Redox signaling during hypoxia in mammalian cells. Redox Biol,2017,13(1): 228–234.
    [17]
    MOLDOGAZIEVA N T, LUTSENKO S V, TERENTIEV A A. Reactive oxygen and nitrogen species–induced protein modifications: implication in carcinogenesis and anticancer therapy. Cancer Res,2018,78(21): 6040–6047. doi: 10.1158/0008-5472.CAN-18-0980
    [18]
    REN X, ZOU L, ZHANG X, et al. Redox signaling mediated by thioredoxin and glutathione systems in the central nervous system. Antioxid Redox Signal,2017,27(13): 989–1010. doi: 10.1089/ars.2016.6925
    [19]
    BEGAS P, LIEDGENS L, MOSELER A, et al. Glutaredoxin catalysis requires two distinct glutathione interaction sites. Nat Commun,2017,8(1): 1–13. doi: 10.1038/s41467-016-0009-6
    [20]
    ELKO E A, CUNNIFF B, SEWARD D J, et al. Peroxiredoxins and beyond; redox systems regulating lung physiology and disease. Antioxid Redox Signal,2019,31(14): 1070–1091. doi: 10.1089/ars.2019.7752
    [21]
    SHANMUGASUNDARAM K, NAYAK B, FRIEDRICHS W, et al. NOX4 functions as a mitochondrial energetic sensor coupling cancer metabolic reprogramming to drug resistance. Nat Commun, 2017, 8(1): 997[2020-04-20]. https://www.nature.com/articles/s41467-017-01106-1. doi: 10.1038/s41467-017-01106-1.
    [22]
    WANG Y, ZHOU W, WANG J, et al. Arginine methylation of MDH1 by CARM1 inhibits glutamine metabolism and suppresses pancreatic cancer. Mol Cell,2016,64(4): 673–687. doi: 10.1016/j.molcel.2016.09.028
    [23]
    FIORANI M, DE SANCTIS R, SCARLATTI F, et al. Dehydroascorbic acid irreversibly inhibits hexokinase activity. Mol Cell Biochem,2000,209(1): 145–153. doi: 10.1023/a:1007168032289
    [24]
    HENEBERG P. Redox regulation of hexokinases. Antioxid Redox Signal,2019,30(3): 415–442. doi: 10.1089/ars.2017.7255
    [25]
    DUMONT S, BYKOVA N, PELLETIER G, et al. Arabidopsis thaliana cytosolic triosephosphate isomerase from is reversibly modified by glutathione on cysteines 127 and 218. Front Plant Sci, 2016, 7: 1942[2020-04-20]. https://www.frontiersin.org/articles/10.3389/fpls.2016.01942/full. doi: 10.3389/fpls.2016.01942.
    [26]
    YUN J, MULLARKY E, LU C, et al. Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH. Science,2015,350(6266): 1391–1396. doi: 10.1126/science.aaa5004
    [27]
    MALLER C, SCHR DER E, EATON P. Glyceraldehyde 3-phosphate dehydrogenase is unlikely to mediate hydrogen peroxide signaling: studies with a novel anti-dimedone sulfenic acid antibody. Antioxid Redox Signal,2011,14(1): 49–60. doi: 10.1089/ars.2010.3149
    [28]
    PERALTA D, BRONOWSKA A, MORGAN B, et al. A proton relay enhances H2O2 sensitivity of GAPDH to facilitate metabolic adaptation. Nat Chem Biol,2015,11(2): 156–163. doi: 10.1038/nchembio.1720
    [29]
    YANG S, ZHAI Q. Cytosolic GAPDH: a key mediator in redox signal transduction in plants. Biologia Plantarum,2017,61(3): 417–426. doi: 10.1007/s10535-017-0706-y
    [30]
    REISZ J A, WITHER M J, DZIECIATKOWSKA M, et al. Oxidative modifications of glyceraldehyde 3-phosphate dehydrogenase regulate metabolic reprogramming of stored red blood cells. Blood,2016,128(12): 32–42. doi: 10.1182/blood-2016-05-714816
    [31]
    GERSZON J, RODACKA A. Oxidatively modified glyceraldehyde-3-phosphate dehydrogenase in neurodegenerative processes and the role of low molecular weight compounds in counteracting its aggregation and nuclear translocation. Ageing Res Rev,2018,48(1): 21–31.
    [32]
    HAY N. Reprogramming glucose metabolism in cancer: can it be exploited for cancer therapy? Nat Rev Cancer,2016,16(10): 635–649. doi: 10.1038/nrc.2016.77
    [33]
    KIM H J, LEE H-R, KIM C S, et al. Investigation of protein expression profiles of erythritol-producing Candida magnoliae in response to glucose perturbation. Enzyme Microb Technol,2013,53(3): 174–180. doi: 10.1016/j.enzmictec.2013.03.016
    [34]
    ANASTASIOU D, POULOGIANNIS G, ASARA J M, et al. Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses. Science,2011,334(6060): 1278–1283. doi: 10.1126/science.1211485
    [35]
    HURD T, COLLINS Y, ABAKUMOVA I, et al. Inactivation of pyruvate dehydrogenase kinase 2 by mitochondrial reactive oxygen species. J Biol Chem,2012,287(42): 35153–35160. doi: 10.1074/jbc.M112.400002
    [36]
    LARSEN F J, SCHIFFER T A, ØRTENBLAD N, et al. High‐intensity sprint training inhibits mitochondrial respiration through aconitase inactivation. FASEB J,2016,30(1): 417–427. doi: 10.1096/fj.15-276857
    [37]
    RÖHRIG F, SCHULZE A. The multifaceted roles of fatty acid synthesis in cancer. Nat Rev Cancer,2016,16(11): 732–749. doi: 10.1038/nrc.2016.89
    [38]
    WANG Y J, BIAN Y, LUO J, et al. Cholesterol and fatty acids regulate cysteine ubiquitylation of ACAT2 through competitive oxidation. Nat Cell Biol,2017,19(7): 808–819. doi: 10.1038/ncb3551
    [39]
    LI X, WANG Z, ZHENG Y, et al. Nuclear receptor Nur77 facilitates melanoma cell survival under metabolic stress by protecting fatty acid oxidation. Mol Cell,2018,69(3): 480–492. doi: 10.1016/j.molcel.2018.01.001
    [40]
    ZMIJEWSKI J W, BANERJEE S, BAE H, et al. Exposure to hydrogen peroxide induces oxidation and activation of AMP-activated protein kinase. J Biol Chem,2010,285(43): 33154–33164. doi: 10.1074/jbc.M110.143685
    [41]
    ZHANG C, HAWLEY S, ZONG Y, et al. Fructose-1, 6-bisphosphate and aldolase mediate glucose sensing by AMPK. Nature,2017,548(7665): 112–116. doi: 10.1038/nature23275
    [42]
    SHAO D, OKA S, LIU T, et al. A redox-dependent mechanism for regulation of AMPK activation by Thioredoxin1 during energy starvation. Cell Metab,2014,19(2): 232–245. doi: 10.1016/j.cmet.2013.12.013
    [43]
    XIE N, YUAN K, ZHOU L, et al. PRKAA/AMPK restricts HBV replication through promotion of autophagic degradation. Autophagy,2016,12(9): 1507–1520. doi: 10.1080/15548627.2016.1191857
    [44]
    REDDY S, JONES A, CROSS C, et al. Inactivation of creatine kinase by S-glutathionylation of the active-site cysteine residue. Biochem J,2000,347(3): 821–827. doi: 10.1042/bj3470821
    [45]
    NIU W, WANG J, QIAN J, et al. Allosteric control of human cystathionine beta-synthase activity by a redox active disulfide bond. J Biol Chem,2018,293(7): 2523–2533. doi: 10.1074/jbc.RA117.000103
    [46]
    NIU W N, YADAV P K, ADAMEC J, et al. S-glutathionylation enhances human cystathionine beta-synthase activity under oxidative stress conditions. Antioxid Redox Signal,2015,22(5): 350–361. doi: 10.1089/ars.2014.5891
    [47]
    SATO H, TAMBA M, ISHII T, et al. Cloning and expression of a plasma membrane cystine/glutamate exchange transporter composed of two distinct proteins. J Biol Chem,1999,274(17): 11455–11458. doi: 10.1074/jbc.274.17.11455
    [48]
    PAUL B, SBODIO J, SNYDER S. Cysteine metabolism in neuronal redox homeostasis. Trends Pharmacol Sci,2018,39(5): 513–524. doi: 10.1016/j.tips.2018.02.007
    [49]
    ALDINI G, ALTOMARE A, BARON G, et al. N-Acetylcysteine as an antioxidant and disulphide breaking agent: the reasons why. Free Radic Res,2018,52(7): 751–762. doi: 10.1080/10715762.2018.1468564
    [50]
    BACKUS K, CORREIA B, LUM K, et al. Proteome-wide covalent ligand discovery in native biological systems. Nature,2016,534(7608): 570–574. doi: 10.1038/nature18002
    [51]
    BAR-PELED L, KEMPER E, SUCIU R, et al. Chemical proteomics identifies druggable vulnerabilities in a genetically defined cancer. Cell,2017,171(3): 696–709. doi: 10.1016/j.cell.2017.08.051
    [52]
    HOGG P J. Targering allosteric disulfide bonds in cancer. Nat Rev Cancer,2013,13(6): 425–431. doi: 10.1038/nrc3519
    [53]
    VAN DER REEST J, LILLA S, ZHENG L, et al. Proteome-wide analysis of cysteine oxidation reveals metabolic sensitivity to redox stress. Nat Commun, 2018, 9(1): 1581[2020-04-20]. https://www.nature.com/articles/s41467-018-04003-3. doi: 10.1038/s41467-018-04003-3.
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