ETK/EZH2信号通路调节膀胱癌细胞侵袭转移的实验研究

项目名称： ETK/EZH2信号通路调节膀胱癌细胞侵袭转移的实验研究

项目编号： No.81202013

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 郭胜杰

作者单位： 中山大学

项目金额： 23万元

中文摘要： 膀胱癌侵袭转移分子机制的研究是泌尿系肿瘤领域的热点。有研究表明表皮酪氨酸蛋白激酶（ETK）高表达于多种肿瘤细胞和组织，并在肿瘤发生和发展过程中发挥重要作用。本课题组首次发现ETK高表达于人膀胱癌细胞和组织，并与膀胱癌细胞的侵袭转移能力相关，进一步研究发现ETK可与一种组蛋白甲基转移酶EZH2相互作用，并增加其蛋白质稳定性，而EZH2是一种甲基化转移酶，其高表达于包括膀胱癌等多种肿瘤组织并与疾病进展相关，因此本课题拟首先应用体内外实验模型探讨ETK/EZH2信号通路在膀胱癌细胞侵袭和转移过程中的作用，其次通过检测ETK对EZH2下游相关蛋白H3K9，H3K27，E-cadherin和TIMP2的调节，阐明ETK调节膀胱癌细胞侵袭转移的分子机制，最后检测ETK/EZH2信号通路相关分子在膀胱癌组织标本中的表达相关性和临床应用价值，进而为膀胱癌寻找新的治疗靶点奠定基础。

中文关键词： 膀胱癌；酪氨酸蛋白激酶；侵袭；转移；

英文摘要： The study of migration and metastasis of bladder cancer is one of the most hot topic in urologic cancer field. Epithelial and endothelial tyrosine kinase （ETK） is one of the tyrosine kinase,which is highly expressed in various tumor and is involved in the development and progression of cancer. We firstly showed that ETK highly expressed in bladder cancer,especially in invasive bladder cancer. we further found that ETK can interacted with histone methyltransferase Enhancer of Zeste 2（EZH2） and stable the protein level of EZH2. As EZH2 play an important role in cancer cell migration and metastasis, we would like to use the in vivo and in vitro model to study the effect and mechanism of ETK/EZH2 signal pathway in the migration and metastasis of bladder cancer cell, and further test the H3K9, H3K27, E-cadherin and RUNX3 which are regulated by the EZH2. Finally, we would like to test the ETK, EZH2, p-EZH2, H3K9, H3K27 ,E-cadherin and TIMP2 in human bladder cancer tissue by IHC to figure out the significance of ETK/EZH2 in clinical application and demonstrated the mechanism of ETK/EZH2 pathway in bladder cancer,and finally to work out the noval target of bladder cancer therapy.

英文关键词： bladder cancer；kinase；invasion；metastasis；