β1,6-N-乙酰氨基葡萄糖转移酶5糖基化修饰TGF-β受体参与调控胃癌细胞分化的分子机制及临床意义研究

项目名称： β1,6-N-乙酰氨基葡萄糖转移酶5糖基化修饰TGF-β受体参与调控胃癌细胞分化的分子机制及临床意义研究

项目编号： No.31300671

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 汪学非

作者单位： 复旦大学

项目金额： 25万元

中文摘要： 胃癌的预后与分化程度密切相关。我们前期研究发现N-糖基化修饰酶β 1,6-N-乙酰氨基葡萄糖转移酶V（MGAT5）在胃癌组织中的表达与分化呈负相关，高表达MGAT5患者预后好，提示其可能通过改变肿瘤组织中N-糖基化修饰状态调控分化进而影响预后。TGF-β信号通路在细胞分化过程中发挥重要作用，其受体的N-糖基化修饰可增加受体膜稳定性进而增强信号活化程度，MGAT5介导的TGF-β受体N-糖基化修饰可能在TGF-β信号通路的活化中起重要作用。本项目以胃癌组织和细胞及其异常表达的MGAT5为研究对象，从MGAT5调控细胞分化和肿瘤糖生物学的角度出发,研究MGAT5糖基化修饰TGF-β受体的分子机制及功能意义。构建MGAT5糖基化修饰TGF-β受体致其异常活化参与细胞分化与胃癌发生发展的分子调控和干预治疗模型，为开发针对N-糖基化修饰的分子靶向药物及建立MGAT5对胃癌预后的分子分型模式奠定基础。

中文关键词： 胃癌；肿瘤微环境；C型凝集素样受体2；分子分型；预后

英文摘要： The prognosis of gastric cancer correlated greatly with tumor differentiation.Our previously study showed β1,6-N-acetylglucosaminyltransferase V (MGAT5) has a negative correlation with gastric tumor cell differentiation using high-throughput tissue microarrays and find that high MGAT5 expression has better prognosis indicating MGAT5 was highly related to tumor cell differentiation and can be used as a prognostic marker. Aberrant MGAT5 expression in malignant tissues has been reported to be involved in the development of various cancers and their progression.MGAT5 can modifies the size and N-Glycans branching of glycoproteins in tumor microenvironment, especially the secreted proteins and membrane receptor proteins that have important functions in proliferation、differentiation、survive、anti-apoptosis etc. Transforming growth factor-β(TGFβ) signal plays a pivotal role in cell differentiation. The location of TGF-β receptor on cell membrane are key determinants of signal activity. Galectins are N-acetyllactosamine binding proteins that can bind the N-glycans of glycoprotein. Galectin 3 cross linked N-Glycans on transforming growth factor-β receptors at the cell surface and delayed their removal by constitutive endocytosis. As such, the lattice of interactions resulting from galectin/glycoprotein crosslinking lim

英文关键词： gastric cancer；tumor microenvironment；CLEC2；molecular classification；prognosis