USP9X/β-catenin互相作用促结肠癌上皮间质转化的机制研究

项目名称： USP9X/β-catenin互相作用促结肠癌上皮间质转化的机制研究

项目编号： No.81201933

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： 杨波

作者单位： 中国人民解放军广州军区武汉总医院

项目金额： 23万元

中文摘要： 结肠癌上皮间质转化（EMT）与侵袭转移密切相关，细胞骨架蛋白β-连环素（β-catenin）是细胞内重要的信号转导分子，其在细胞核中高表达可以促进肿瘤细胞EMT和侵袭转移，但β-catenin转位入核增加的机制尚未明确。我们前期研究发现，结肠癌组织中去泛素化酶USP9X高表达，与β-catenin的表达存在显著相关关系，免疫共沉淀提示两种蛋白存在相互作用。因此，本项目拟以结肠癌为研究对象，首先检测USP9X/β-catenin的表达对肿瘤细胞EMT和结肠癌侵袭转移的影响；其次探讨USP9X去泛素化稳定β-catenin，增加其核转位在EMT中的作用；再次从分子水平探讨β-catenin/TCF4/LEF-1转录复合体诱导MMP-9高表达与肿瘤细胞EMT的关系；旨在阐释USP9X/β-catenin相互作用促进结肠癌细胞EMT，增强其侵袭转移能力的机制，为探索结肠癌治疗的新靶点奠定理论基础。

中文关键词： 结肠癌；上皮间质转化；去泛素化酶；β-连环素；泛素化

英文摘要： The epithelial-mesenchymal transition(EMT) of colon cancer cell is closely related with tumor invasion and metastasis. Cytoskeletal protein β-catenin is a crucial signal transduction molecule in cell. It promotes EMT and tumor invasion and metastasis if it is highly expressed in cell nucleus. But the mechanism of β-catenin transferring to cell nucleus is still inconclusive. In our previous study, we found that the expression of USP9X was higher in the colon cancer tissues than in normal colon mucosa. Increased USP9X expression significantly correlated with increased β-catenin protein in colon carcinomas.USP9X interacted with β-catenin by immunoprecipitation. So we will take colon cancer as the target to explore in this study. Firstly, the correlation between expression of USP9X/β-catenin and EMT, tumor invasion and metastasis will be analyzed in colon cancer tissues. Secondly, the deubiquitinase USP9X stabilizing β-catenin which may accumulate and translocate into the cell nucleus will be examined. Thirdly, the transcription complex β-catenin/TCF4/LEF-1 upregulating MMP-9 trascription level of tumor cell will be detected. Thus, colon cancer cells will be lead to EMT and the ability of invasion and metastasis will be enhanced. This project aims to reveal the new molecular mechanisms of EMT in colon carcinoma and

英文关键词： colon cancer；epithelial-mesenchymal transition；deubiquitination enzymes；β-catenin；ubiquitination