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蛋白质O-GlcNAc修饰与肿瘤糖代谢关系的研究进展

张炜琳, 王鑫怡, 严方

张炜琳, 王鑫怡, 严方. 蛋白质O-GlcNAc修饰与肿瘤糖代谢关系的研究进展[J]. 中国药科大学学报, 2019, 50(2): 127-134. DOI: 10.11665/j.issn.1000-5048.20190201
引用本文: 张炜琳, 王鑫怡, 严方. 蛋白质O-GlcNAc修饰与肿瘤糖代谢关系的研究进展[J]. 中国药科大学学报, 2019, 50(2): 127-134. DOI: 10.11665/j.issn.1000-5048.20190201
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ZHANG Weilin, WANG Xinyi, YAN Fang. Advances of relationship between protein O-GlcNAcylation and glucose metabolism in tumors[J]. Journal of China Pharmaceutical University, 2019, 50(2): 127-134. DOI: 10.11665/j.issn.1000-5048.20190201
Citation: ZHANG Weilin, WANG Xinyi, YAN Fang. Advances of relationship between protein O-GlcNAcylation and glucose metabolism in tumors[J]. Journal of China Pharmaceutical University, 2019, 50(2): 127-134. DOI: 10.11665/j.issn.1000-5048.20190201
shu

蛋白质O-GlcNAc修饰与肿瘤糖代谢关系的研究进展

  • 中国药科大学药物分析教研室

Advances of relationship between protein O-GlcNAcylation and glucose metabolism in tumors

摘要

    摘要
  • 摘要: 蛋白质O-GlcNAc糖基化是指单个N-乙酰葡萄糖胺(N-acetylglucosamine，GlcNAc)分子连接在蛋白质丝氨酸或苏氨酸的羟基氧原子上的一种翻译后修饰。O-GlcNAc糖基化广泛存在于转录因子、代谢通路上的激酶以及细胞质的部分酶中，影响细胞的转录、信号的传导和细胞的代谢等生命进程。肿瘤的异常糖代谢是近年来肿瘤发病机制和治疗靶点研究领域的热点。O-GlcNAc糖基化通过影响代谢通路上激酶的活性进而调控肿瘤细胞的糖代谢，与肿瘤的糖代谢密切相关，被认为是肿瘤产生发展的潜在原因之一。本文就O-GlcNAc修饰在肿瘤葡萄糖摄取、糖酵解、戊糖磷酸途径及三羧酸循环等研究中的进展进行综述，为研发靶向O-GlcNAc修饰的抗肿瘤靶点及药物提供理论参考。
    Abstract: O-GlcNAcylation is the addition of a single N-acetylglucosamine(GlcNAc)moiety to the hydroxyl groups of serine or threonine residues of nuclear and cytoplasmic proteins. The transcription factors, kinases of the metabolic pathways and some cytoplasmic enzymes can be O-GlcNAcylated to affect cell transcription, signal transduction, cell metabolism and other biological functions. Abnormal glucose metabolism of tumors has been a hotspot in the research field of tumor pathogenesis and therapeutic targets recently. O-GlcNAclation regulates the glucose metabolism of tumor by affecting the activity of kinases in the metabolic pathway, which is closely associated with the abnormal glucose metabolism of tumor. The abnormal O-GlcNAcylation is one of the potential reasons of cancer. In this review, in order to provide a theoretical reference for developing anti-tumor targets and drugs targeting O-GlcNAc modification, we briefly summarized how O-GlcNAcylation regulated glucose metabolism on glucose metabolism, glucose uptake, glycolysis, pentose phosphate pathway and tricarboxylic acid cycle in cancer cell.
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  • [1] Uhlen M,Fagerberg L,Hallstrom BM,et al.Tissue-based map of the human proteome[J].Science,2015,347(6220):1260419.
    [2] Torres MP,Dewhurst H,Sundararaman N.Proteome-wide structural analysis of PTM hotspots reveals regulatory elements predicted to impact biological function and disease[J].Mol Cell Proteomics,2016,15(11):3513-3528.
    [3] Cattaneo A,Chirichella M.Targeting the post-translational proteome with intrabodies[J].Trends Biotechnol,2018,Epub ahead of print.
    [4] Cummings RD,Pierce JM.The challenge and promise of glycomics[J].Chem Biol,2014,21(1):1-15.
    [5] Tan EP,Mcgreal SR,Graw S,et al.Sustained O-GlcNAcylation reprograms mitochondrial function to regulate energy metabolism[J].J Biol Chem,2017,292(36):14940-14962.
    [6] Park S,Lee Y,Pak JW,et al.O-GlcNAc modification is essential for the regulation of autophagy in drosophila melanogaster[J].Cell Mol Life Sci,2015,72(16):3173-3183.
    [7] Akan I,Stichelen SOV,Bond MR,et al.Nutrient-driven O-GlcNAc in proteostasis and neurodegeneration[J].J Neurochem,2018,144(1):7-34.
    [8] Abramowitz LK,Hanover JA.T cell development and the physiological role of O-GlcNAc[J].FEBS Lett,2018,592(23):3943-3949.
    [9] De Jesus T,Shukla S,Ramakrishnan P.Too sweet to resist:control of immune cell function by O-GlcNAcylation[J].Cell Immunol,2018,333:85-92.
    [10] Deberardinis RJ,Thompson CB.Cellular metabolism and disease:What do metabolic outliers teach us[J]?Cell,2012,148(6):1132-1144.
    [11] Galhardo M,Sinkkonen L,Berninger P,et al.Integrated analysis of transcript-level regulation of metabolism reveals disease-relevant nodes of the human metabolic network[J].Nucleic Acids Res,2014,42(3):1474-1496.
    [12] Webb BA,Forouhar F,Szu FE,et al.Structures of human phosphofructokinase-1 and atomic basis of cancer-associated mutations[J].Nature,2015,523(7558):111-114.
    [13] Ouyang XS,Han SN,Zhang JY,et al.Digoxin suppresses pyruvate kinase M2-promoted HIF-1α transactivation in steatohepatitis[J].Cell Metab,2018,27(5):1156.
    [14] Rao XJ,Duan XT,Mao WM,et al.O-GlcNAcylation of G6PD promotes the pentose phosphate pathway and tumor growth[J].Nat Commun,2015,6:8468.
    [15] Li TL,Li XH,Attri KS,et al.O-GlcNAc transferase links glucose metabolism to MAVS-mediated antiviral innate immunity[J].Cell Host Microbe,2018,24(6):791-803.
    [16] Yang AQ, Li DY, Chi LL, et al. Validation,identification,and biological consequences of the site-specific O-GlcNAcylation dynamics of carbohydrate-responsive element-binding protein(ChREBP)[J].Mol Cell Proteomics,2017,16(7):1233-1243.
    [17] Hardiville S,Hart GW.Nutrient regulation of signaling,transcription,and cell physiology by O-GlcNAcylation[J].Cell Metab,2014,20(2):208-213.
    [18] Yang XY,Qian KV.Protein O-GlcNAcylation:emerging mechanisms and functions[J].Nat Rev Mol Cell Biol,2017,18(7):452-465.
    [19] Banerjee PS,Lagerlof O,Hart GW.Roles of O-GlcNAc in chronic diseases of aging[J].Mol Aspects Med,2016,51:1-15.
    [20] Tramutola A,Sharma N,Barone E,et al.Proteomic identification of altered protein O-GlcNAcylation in a triple transgenic mouse model of Alzheimer′s disease[J].BBA-Mol Basis Dis,2018,1864(10):3309-3321.
    [21] Torres CR,Hart GW.Topography and polypeptide distribution of terminal N-Acetylglucosamine residues on the surfaces of intact lymphocytes- fvidence for O-linked glcnac[J].J Biol Chem,1984,259(5):3308-3317.
    [22] Zachara NE.Critical observations that shaped our understanding of the function(s)of intracellular glycosylation(O-GlcNAc)[J].FEBS Lett,2018,592(23):3950-3975.
    [23] Miguez JSG,Dela Justina V,Bressan AFM,et al.O-Glycosylation with O-linked beta-N-acetylglucosamine increases vascular contraction:possible modulatory role on interleukin-10 signaling pathway[J].Life Sci,2018,209:78-84.
    [24] Marotta NP,Lin YH,Lewis YE,et al.O-GlcNAc modification blocks the aggregation and toxicity of the protein alpha-synuclein associated with Parkinson′s disease[J].Nat Chem,2015,7(11):913-920.
    [25] Sullivan LB,Gui DY,Heiden MGV.Altered metabolite levels in cancer:implications for tumour biology and cancer therapy[J].Nat Rev Cancer,2016,16(11):680-693.
    [26] Pavlova NN,Thompson CB.The emerging hallmarks of cancer metabolism[J].Cell Metab,2016,23(1):27-47.
    [27] Goodpaster BH,Sparks LM.Metabolic flexibility in health and disease[J].Cell Metab,2017,25(5):1027-1036.
    [28] Kalyanaraman B,Cheng G,Hardy M,et al.A review of the basics of mitochondrial bioenergetics,metabolism,and related signaling pathways in cancer cells:therapeutic targeting of tumor mitochondria with lipophilic cationic compounds[J].Redox Biology,2018,14:316-327.
    [29] Elaskalani O, Falasca M, Moran N, et al. The role of platelet-derived ADP and ATP in promoting pancreatic cancer cell survival and gemcitabine resistance[J].Cancers,2017,9(10):E142.
    [30] Warburg O,Wind F,Negelein E.The metabolism of tumors in the body[J].J Gen Physiol,1927,8(6):519-530.
    [31] Barron CC,Bilan PJ,Tsakiridis T,et al.Facilitative glucose transporters:implications for cancer detection,prognosis and treatment[J].Metabolism,2016,65(2):124-139.
    [32] Zhou Q,Yang XZ,Xiong MR,et al.Chloroquine increases glucose uptake via enhancing GLUT4 translocation and fusion with the plasma membrane in L6 cells[J].Cell Physiol Biochem,2016,38(5):2030-2040.
    [33] Buse MG,Robinson KA,Marshall BA,et al.Enhanced O-GlcNAc protein modification is associated with insulin resistance in GLUT1-overexpressing muscles[J].Am J Physiol Endocrinol Metab,2002,283(2):E241-E250.
    [34] Park SY,Ryu JW,Lee W.O-GlcNAc modific ation on IRS-1 and Akt2 by PUGNAc inhibits their phosphorylation and induces insulin resistance in rat primary adipocytes[J].Exp Mol Med,2005,37(3):220-229.
    [35] Masoud GN, Li W. HIF-1 alpha pathway: role, regulation and intervention for cancer therapy[J].Acta Pharm Sin B,2015,5(5):378-389.
    [36] Ferrer CM,Lynch TP,Sodi VL,et al.O-GlcNAcylation regulates cancer metabolism and survival stress signaling via regulation of the HIF-1 pathway[J].Mol Cell,2014,54(5):820-831.
    [37] Sodi VL,Bacigalupa ZA,Ferrer CM,et al.Nutrient sensor O-GlcNAc transferase controls cancer lipid metabolism via SREBP-1 regulation[J].Oncogene,2018,37(7):924-934.
    [38] Shimizu M,Tanaka N.IL-8-induced O-GlcNAc modification via GLUT3 and GFAT regulates cancer stem cell-like properties in colon and lung cancer cells[J].Oncogene,2018.38(9):1520-1533.
    [39] Semenza GL.Hypoxia-inducible factors:coupling glucose metabolism and redox regulation with induction of the breast cancer stem cell phenotype[J].EMBO J,2017,36(3):252-259.
    [40] Yi W,Clark PM,Mason DE,et al.Phosphofructokinase 1 glycosylation regulates cell growth and metabolism[J].Science,2012,337(6097):975-980.
    [41] Kishore M,Cheung KCP,Fu HM,et al.Regulatory T cell migration is dependent on glucokinase-mediated glycolysis[J].Immunity,2017,47(5):875-889.
    [42] Baldini SF,Steenackers A,Olivier-Van Stichelen S,et al.Glucokinase expression is regulated by glucose through O-GlcNAc glycosylation[J].Biochem Biophys Res Commun,2016,478(2):942-948.
    [43] Lee JH,Liu R,Li J,et al.Stabilization of phosphofructokinase 1 platelet isoform by AKT promotes tumorigenesis[J].Nat Commun,2017,8(1):949.
    [44] Stincone A,Prigione A,Cramer T,et al.The return of metabolism:biochemistry and physiology of the pentose phosphate pathway[J].Biol Rev,2015,90(3):927-963.
    [45] Wang Y,Liu J,Jin X,et al.GlcNAcylation destabilizes the active tetrameric PKM2 to promote the Warburg effect[J].Proc Natl Acad Sci U S A,2017,114(52):13732-13737.
    [46] Cieniewski-Bernard C,Bastide B,Lefebvre T,et al.Identification of O-linked N-acetylglucosamine proteins in rat skeletal muscle using two-dimensional gel electrophoresis and mass spectrometry[J].Mol Cell Proteomics,2004,3(6):577-585.
    [47] Woo CM,Lund PJ,Huang AC,et al.Mapping and quantification of over 2000 O-linked glycopeptides in activated human T cells with isotope-targeted glycoproteomics(Isotag)[J].Mol Cell Proteomics,2018,17(4):764-775.
    [48] Yehezkel G,Cohen L,Kliger A,et al.O-Linked beta-N-Acetylglucosaminylation(O-GlcNAcylation)in primary and metastatic colorectal cancer clones and effect of N-acetyl-beta-D-glucosaminidase silencing on cell phenotype and transcriptome[J].J Biol Chem,2012,287(34):28755-28769.
    [49] Lucena MC,Carvalho-Cruz P,Donadio JL,et al.Epithelial mesenchymal transition induces aberrant glycosylation through hexosamine biosynthetic pathway activation[J].J Biol Chem,2016,291:12917-12929.
    [50] Hui S,Ghergurovich JM,Morscher RJ,et al.Glucose feeds the TCA cycle via circulating lactate[J].Nature,2017,551(7678):115-118.
    [51] Tan EP,Villar MT,E L,et al.Altering O-linked beta-N-Acetylglucosamine cycling disrupts mitochondrial function[J].J Biol Chem,2014,289(21):14719-14730.
    [52] Ma JF,Banerjee P,Whelan SA,et al.Comparative proteomics reveals dysregulated mitochondrial O-GlcNAcylation in diabetic hearts[J].J Proteome Res,2016,15(7):2254-2264.
    [53] Wang T,Yu QJ,Li JJ,et al.O-GlcNAcylation of fumarase maintains tumour growth under glucose deficiency[J].Nat Cell Biol,2017,19(7):833-843.
    [54] Jin L,Alesi GN,Kang S.Glutaminolysis as a target for cancer therapy[J].Oncogene,2016,35(28):3619-3625.
    [55] Altman BJ,Stine ZE,Dang CV.From Krebs to clinic:glutamine metabolism to cancer therapy[J].Nat Rev Cancer,2016,16(12):773-773.
    [56] Park HW,Kim YC,Yu B,et al.Alternative wnt signaling activates YAP/TAZ[J].Cell,2015,162(4):780-794.
    [57] Kim W,Khan SK,Gvozdenovic-Jeremic J,et al.Hippo signaling interactions with wnt/beta-catenin and notch signaling repress liver tumorigenesis[J].J Clin Invest,2017,127(1):137-152.
    [58] Lee DH,Park JO,Kim TS,et al.LATS-YAP/TAZ controls lineage specification by regulating TGFbeta signaling and Hnf4alpha expression during liver development[J].Nat Commun,2016,7:11961.
    [59] Zhang X,Qiao YX,Wu Q,et al.The essential role of YAP O-GlcNAcylation in high-glucose-stimulated liver tumorigenesis[J].Nat Commun,2017,8:15280.
    [60] Clark PM,Dweck JF,Mason DE,et al.Direct in-gel fluorescence detection and cellular imaging of O-GlcNAc-modified proteins[J].J Am Chem Soc,2008,130(35):11576-11577.
    [61] Sun RC,Denko NC.Hypoxic regulation of glutamine metabolism through HIF1 and SIAH2 supports lipid synthesis that is necessary for tumor growth[J].Cell Metab,2014,19(2):285-292.
    [62] Ren NSX, Ji M, Tokar EJ, et al. Haploinsufficiency of SIRT1 enhances glutamine metabolism and promotes cancer development[J].Curr Biol,2017,27(4):483-494.
    [63] Sun HB.Drug discovery based on pharmacological interference with glycometabolism[J].J China Pharm Univ(中国药科大学学报),2006,37(1):1-8.
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  • 刊出日期:  2019-04-24

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