CtBP2与SOX-2相互作用参与食管鳞状细胞癌发病机制的研究

项目名称： CtBP2与SOX-2相互作用参与食管鳞状细胞癌发病机制的研究

项目编号： No.81502055

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 管程齐

作者单位： 南通大学

项目金额： 18万元

中文摘要： 转录辅阻遏因子CtBP2能够与转录因子相互作用影响参与肿瘤的发生发展。课题前期研究显示CtBP2的表达与食管癌的增殖、转移及预后密切相关；并发现转录因子SOX-2是CtBP2一个新的相互作用蛋白；干扰CtBP2后发现SOX-2下游靶基因S100A1表达显著上调。CtBP2、SOX-2、S100A1被报道在肿瘤细胞转移过程均发挥重要作用。基于此，本课题提出在食管癌中CtBP2与SOX-2相互作用调节S100A1的转录参与食管癌发病机制的假说。课题组拟检测食管癌组织中CtBP2、SOX-2、S100A1表达的相关性及对预后的影响；分析CtBP2与SOX-2的相互作用及其结构域以及该作用对S100A1的转录调节，并研究此机制对食管癌细胞增殖、迁移的影响；最后通过裸鼠成瘤模型在体内水平验证该机制。本研究将揭示CtBP2/SOX-2在食管癌发生发展中的分子机制，为食管癌的治疗寻找新的调控靶点。

中文关键词： 食管肿瘤；羧基末端结合蛋白-2；性别决定区Y-box2；转录；转移

英文摘要： As a transcription repressor, CtBP2 can interact with transcription factors and participate in the process of tumor development. In our preliminary work, we have revealed the direct relationships between the expression of CtBP2 and the cell proliferation, metastasis and prognosis of Esophageal Squamous Cell Carcinoma (ESCC).We show the transcription factors SOX-2 is a new interaction of CtBP2. RNA interference-mediated knockdown of CtBP2 decreased the expression of S100A1, which is the target gene of SOX-2.CtBP2，SOX-2 and S100A1 were previously reported playing an important role in the process of tumor metastasis. Based on this, we propose CtBP2 can interact with SOX-2 to regulate transcriptional activities of S100A1 ,thus promoting ESCC procession. First, we intend to analyze the relationship between CtBP2,SOX-2 and S100A1expression and clinicopathological parameters in clinical ESCC tissue samples. Then we analyze the interaction of CtBP2 and SOX-2 and its domains, and to study the impact of the mechanism of S100A1 transcriptional activity and cell proliferation and migration of ESCC. Finally, we study the impact of CtBP2/SOX-2 on the development of ESCC in nude mice models. Carrying out this project will help to elucidate the molecular mechanisms of CtBP2/SOX-2, and help to understand the role of this mechanism in the development of ESCC, and provide a new theoretical basis for the targeted treatment of ESCC.

英文关键词： ESCC;CtBP2;SOX-2;transcription;metastasis