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作 者:舒健[1] 于汉杰[1] 刘夏薇[1] 张旦旦[1] 李铮[1]
机构地区:[1]西北大学生命科学学院功能糖组学实验室,西安710069
出 处:《生物化学与生物物理进展》2016年第5期449-460,共12页Progress In Biochemistry and Biophysics
基 金:国家自然科学基金基地建设能力提高项目(J1210063)资助~~
摘 要:胃癌是一类高发病率和高死亡率的恶性肿瘤.研究表明,癌前感染与胃癌的发生发展过程始终伴随着蛋白糖基化的异常.例如在癌前感染阶段糖蛋白糖链发挥的作用:在感染阶段,幽门螺杆菌(Helicobacter pylori,H.pylori)吸附导致的唾液酸化路易斯X抗原的上调,增强了H.pylori的吸附作用使其在胃部定殖并诱发持续的炎症反应;在慢性胃炎和肠上皮化生阶段唾液酸化的Tn抗原表达上调.胃癌发生发展过程中涉及到了血清、组织、细胞中的蛋白糖基化的改变,如核心岩藻糖基化N-糖链表达的下调,β1,6-连接的N-乙酰葡糖胺分支型N-糖链的增加,以及细胞黏附分子糖基化的改变.本文综述了胃癌相关糖蛋白糖链研究的最新进展,阐述了糖基化在胃癌的发生发展中发挥的重要作用及其作为胃癌早期生物标志物与药物靶点的潜在临床应用价值.Gastric cancer(GC) is one of the most common malignant tumors with high incidence and mortality in the world. Currently, the alterations of protein glycosylation has been extensively reported during gastric carcinogenesis and cancer progression. In the initial steps of the process of gastric carcinogenesis, Helicobacter pylori(H. pylori) uses glycan to adhere the host mucosa, which leads to the increase of sialyl-Lewisxlevel. Further up-regulation of the H. pylori colonization induces sustained inflammation in stomach. In the process of chronic atrophic gastritis and intestinal metaplasia, sialyl-Tn antigen showed a significant up-regulation. Moreover, in GC,the abnormal protein glycosylation emerges in serum and tissue from GC patients as well as GC cell lines, such as down-regulation of core fucosylated N-glycan and up-regulation of β1, 6-Glc NAc branched N-glycan were discovered. It also shows that the altered glycosylation of adhesin contributes to the development of GC. This review summarizes the recent progress of protein glycosylation in GC and the important functions of glycosylation in the carcinogenesis and development. Finally, the application values of the alterations of glycosylation, such as potential biomarker for early diagnosis and drug target designing were discussed.
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