蛋白质糖基化在肺癌发生发展中的作用

doi:10.3969/j.issn.1009-976X.2022.04.021

摘要/Abstract

摘要： 肺癌发病率居恶性肿瘤第二位,病死率居首位,早期发现可以大大提高患者的生存率。然而,缺乏可靠的血液生物标志物仍然是早期诊断的主要因素。最近的研究表明,异常的蛋白质糖基化在肿瘤生长、侵袭、转移等方面发挥重要作用,并与肺癌的预后密切相关,肺癌相关的蛋白质表达与调控具有特征性的糖基化模式,检测气管分泌物及血液中的糖蛋白有望成为早期诊断肺癌的生物标记物。本文就异常蛋白糖基化在肺癌进展中的作用进行综述。

关键词: 肺癌, 糖基化, 靶向治疗, 生物标志物

Abstract: Globally, lung cancer is the second-highest cancer incidence and remains the leading cause of cancer mortality worldwide. Early detection can greatly improve patient survival rates. However, the lack of reliable blood biomarkers remains a major factor in early diagnosis. Recent studies have shown that aberrant glycosylation plays an important role in tumor growth, invasion, and metastasis,and is closely related to the prognosis of lung cancer. The expression and regulation of proteins associated with lung cancer have a characteristic glycosylation pattern, and the detection of glycoproteins in tracheal secretions and blood is expected to be a biomarker for the early diagnosis of lung cancer. This article reviews the role of aberrant protein glycosylation in the progression of lung cancer.

Key words: lung cancer, glycosylation, targeted therapy, biomarker

中图分类号:

R734.2

徐圣善, 王志刚, 卢珠明. 蛋白质糖基化在肺癌发生发展中的作用[J]. 岭南现代临床外科, 2022, 22(04): 428-432.

XU Sheng-shan, WANG Zhi-gang, LU Zhu-ming. The role of protein glycosylation in the development of lung cancer[J]. Lingnan Modern Clinics In Surgery, 2022, 22(04): 428-432.

参考文献

[1] Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021[J]. CA Cancer J Clin, 2021, 71(1):7-33.
[2] Sung H, Ferlay J, Siegel RL, et al.Global Cancer Statistics 2020:GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries[J]. CA Cancer J Clin, 2021, 71(3):209-249.
[3] Fidler MM, Bray F, Soerjomataram I.The global cancer burden and human development:A review[J]. Scand J Public Health, 2018, 46(1):27-36.
[4] Roomi MW, Kalinovsky T, Niedzwiecki A, et al.Modulation of u-PA, MMPs and their inhibitors by a novel nutrient mixture in human lung cancer and mesothelioma cell lines[J]. Int J Oncol, 2013, 42(6):1883-1889.
[5] 陈秋莉, 王莲子, 吴宪, 等. 肿瘤异常糖蛋白在肺癌中的诊断价值[J]. 安徽医科大学学报, 2018, 53(6):960-963.
[6] Ohtsubo K, Marth JD.Glycosylation in cellular mechanisms of health and disease[J]. Cell, 2006, 126(5):855-867.
[7] 高春芳.糖基化:未来可期的新型疾病标志物[J]. 中华检验医学杂志,2022, 45(4):315-317.
[8] Mereiter S, Balmaña M, Campos D, et al.Glycosylation in the Era of Cancer-Targeted Therapy:Where Are We Heading?[J]. Cancer Cell, 2019, 36(1):6-16.
[9] Pinho SS, Reis CA.Glycosylation in cancer:mechanisms and clinical implications[J]. Nat Rev Cancer, 2015, 15(9):540-555.
[10] Rao TD, Fernández-Tejada A, Axelrod A, et al.Antibodies Against Specific MUC16 Glycosylation Sites Inhibit Ovarian Cancer Growth[J]. ACS Chem Biol, 2017, 12(8):2085-2096.
[11] Jian C, Wan H, Bo W, et al.N-glycosylation by N-acetylglucosaminyltransferase V enhances the interaction of CD147/basigin with integrin β1 and promotes HCC metastasis[J]. J Pathol, 2018, 245(1):41-52.
[12] Chakraborty A, Dorsett KA, Trummell HQ, et al.ST6Gal-I sialyltransferase promotes chemoresistance in pancreatic ductal adenocarcinoma by abrogating gemcitabine-mediated DNA damage[J]. J Biol Chem, 2018, 293(3):984-994.
[13] Caldwell SA, Jackson SR, Shahriari KS, et al.Nutrient sensor O-GlcNAc transferase regulates breast cancer tumorigenesis through targeting of the oncogenic transcription factor FoxM1[J]. Oncogene, 2010, 29(19):2831-2842.
[14] Wu YM, Liu CH, Huang MJ, et al.C1GALT1 enhances proliferation of hepatocellular carcinoma cells via modulating MET glycosylation and dimerization[J]. Cancer Res, 2013, 73(17):5580-5590.
[15] Wagner KW, Punnoose EA, Januario T, et al.Death-receptor O-glycosylation controls tumor-cell sensitivity to the proapoptotic ligand Apo2L/TRAIL[J]. Nat Med, 2007, 13(9):1070-1077.
[16] Soesanto YA, Luo B, Jones D, et al.Regulation of Akt signaling by O-GlcNAc in euglycemia[J]. Am JPhysiol Endocrinol Metab, 2008, 295(4):E974-980.
[17] Wells L, Slawson C, Hart GW.The E2F-1 associated retinoblastoma-susceptibility gene product is modified by O-GlcNAc[J]. Amino acids, 2011, 40(3):877-883.
[18] Peixoto A, Relvas-Santos M, Azevedo R, et al.Protein Glycosylation and Tumor Microenvironment Alterations Driving Cancer Hallmarks[J]. Front Oncol, 2019, 9:380.
[19] Kessenbrock K, Plaks V, Werb Z.Matrix metalloproteinases:regulators of the tumor microenvironment[J]. Cell, 2010, 141(1):52-67.
[20] Taga M, Hoshino H, Low S, et al. A potential role for 6-sulfo sialyl Lewis X in metastasis of bladder urothelial carcinoma[J]. Urol Oncol, 2015, 33(11):496.e491-499.
[21] Dosaka-Akita H, Miyoshi E, Suzuki O, et al.Expression of N-acetylglucosaminyltransferase v is associated with prognosis and histology in non-small cell lung cancers[J]. Clin Cancer Res, 2004, 10(5):1773-1779.
[22] 郑军平, 刘洪涛, 杜昱光. O-乙酰氨基葡萄糖(O-GlcNAc)修饰及其生物学功能研究进展[J]. 微生物学报, 2017, 57(8):1141-1151.
[23] Hart GW, Slawson C, Ramirez-Correa G, et al.Cross talk between O-GlcNAcylation and phosphorylation:roles in signaling, transcription, and chronic disease[J]. Ann Rev Biochem, 2011, 80:825-858.
[24] Guo H, Zhang B, Nairn AV, et al.O-Linked N-Acetylglucosamine (O-GlcNAc) Expression Levels Epigenetically Regulate Colon Cancer Tumorigenesis by Affecting the Cancer Stem Cell Compartment via Modulating Expression of Transcriptional Factor MYBL1[J]. J Biol Chem, 2017, 292(10):4123-4137.
[25] Hanover JA, Chen W, Bond MR.O-GlcNAc in cancer:An Oncometabolism-fueled vicious cycle[J]. J Bioenerg Biomembr, 2018, 50(3):155-173.
[26] Slawson C, Copeland RJ, Hart GW.O-GlcNAc signaling:a metabolic link between diabetes and cancer?[J]. Trends Biochem Sci, 2010, 35(10):547-555.
[27] Ma Z, Vosseller K.Cancer metabolism and elevated O-GlcNAc in oncogenic signaling[J]. J Biol Chem, 2014, 289(50):34457-34465.
[28] Lynch TP, Ferrer CM, Jackson SR,et al.Critical role of O-Linked β-N-acetylglucosamine transferase in prostate cancer invasion, angiogenesis, and metastasis[J]. J Biol Chem, 2012, 287(14):11070-11081.
[29] Zhu W, Leber B, Andrews DW.Cytoplasmic O-glycosylation prevents cell surface transport of E-cadherin during apoptosis[J]. EMBO J, 2001, 20(21):5999-6007.
[30] Warburg O.On the origin of cancer cells[J]. Science (New York, NY), 1956, 123(3191):309-314.
[31] Zachara NE, Hart GW.Cell signaling, the essential role of O-GlcNA！[J].Biochim Biophys Acta, 2006, 1761(5-6):599-617.
[32] Mi W, Gu Y, Han C, et al.O-GlcNAcylation is a novel regulator of lung and colon cancer malignancy[J]. Biochim Biophys Acta, 2011, 1812(4):514-519.
[33] Yi W, Clark PM, Mason DE, et al.Phosphofructokinase 1 glycosylation regulates cell growth and metabolism[J]. Science, 2012, 337(6097):975-980.
[34] Sola-Penna M, Da Silva D, Coelho WS,et al.Regulation of mammalian muscle type 6-phosphofructo-1-kinase and its implication for the control of the metabolism[J]. IUBMB life, 2010, 62(11):791-796.
[35] Christofk HR, Vander Heiden MG, Wu N, et al.Pyruvate kinase M2 is a phosphotyrosine-binding protein[J]. Nature, 2008, 452(7184):181-186.
[36] Ralser M, Wamelink MM, Kowald A, et al.Dynamic rerouting of the carbohydrate flux is key to counteracting oxidative stress[J]. J Biol, 2007, 6(4):10.
[37] Ponnusamy MP, Seshacharyulu P, Lakshmanan I, et al.Emerging role of mucins in epithelial to mesenchymal transition[J]. Curr Cancer Drug Targets, 2013, 13(9):945-956.
[38] Inata J, Hattori N, Yokoyama A, et al.Circulating KL-6/MUC1 mucin carrying sialyl Lewisa oligosaccharide is an independent prognostic factor in patients with lung adenocarcinoma[J]. Int J cancer, 2007, 120(12):2643-2649.
[39] Raina D, Kosugi M, Ahmad R, et al.Dependence on the MUC1-C oncoprotein in non-small cell lung cancer cells[J]. Mol Cancer Ther, 2011, 10(5):806-816.
[40] Gao J, McConnell MJ, Yu B, et al. MUC1 is a downstream target of STAT3 and regulates lung cancer cell survival and invasion[J]. Int J Oncol, 2009, 35(2):337-345.
[41] Quoix E, Lena H, Losonczy G, et al.TG4010 immunotherapy and first-line chemotherapy for advanced non-small-cell lung cancer (TIME):results from the phase 2b part of a randomised, double-blind, placebo-controlled, phase 2b/3 trial[J]. Lancet Oncol, 2016, 17(2):212-223.
[42] Zhang L, Gallup M, Zlock L, et al.Pivotal role of MUC1 glycosylation by cigarette smoke in modulating disruption of airway adherens junctions in vitro[J]. J Pathol, 2014, 234(1):60-73.
[43] Becker DJ, Lowe JB.Fucose:biosynthesis and biological function in mammals[J]. Glycobiology, 2003, 13(7):41r-53r.
[44] Wang X, Gu J, Ihara H, et al.Core fucosylation regulates epidermal growth factor receptor-mediated intracellular signaling[J]. J Biol Chem, 2006, 281(5):2572-2577.
[45] Chen CY, Jan YH, Juan YH, et al.Fucosyltransferase 8 as a functional regulator of nonsmall cell lung cancer[J]. Proc Natl Acad Sci U S A, 2013, 110(2):630-635.
[46] Liu YC, Yen HY, Chen CY, et al.Sialylation and fucosylation of epidermal growth factor receptor suppress its dimerization and activation in lung cancer cells[J]. Proc Natl Acad Sci U S A, 2011, 108(28):11332-11337.
[47] Honma R, Kinoshita I, Miyoshi E, etal. Expression of fucosyltransferase 8 is associated with an unfavorable clinical outcome in non-small cell lung cancers[J]. Oncology, 2015, 88(5):298-308.
[48] Yang S, Xia J, Yang Z, et al.Lung cancer molecular mutations and abnormal glycosylation as biomarkers for early diagnosis[J]. Cancer Treat Res Commun,2021, 27:100311.
[49] Fernandes E, Sores J, Cotton S, et al.Esophageal, gastric and colorectal cancers:Looking beyond classical serological biomarkers towards glycoproteomics-assisted precision oncology[J]. Theranostics, 2020, 10(11):4903-4928.
[50] Thomas D, Rathinavel AK, Radhakrishnan P.Altered glycosylation in cancer:A promising target for biomarkers and therapeutics[J]. Biochimica et biophysica acta Reviews on cancer, 2021, 1875(1):188464.
[51] Adamczyk B, Tharmalingam T, Rudd PM.Glycans as cancer biomarkers[J]. Biochim Biophys Acta. , 2012, 1820(9):1347-1353.