EADIA调节抑癌基因DCC凋亡通路的分子机制研究

项目名称： EADIA调节抑癌基因DCC凋亡通路的分子机制研究

项目编号： No.81672722

项目类型： 面上项目

立项/批准年度： 2017

项目学科： 医药、卫生

项目作者： 陈强

作者单位： 四川大学

项目金额： 25万元

中文摘要： DCC是一个抑癌基因，在70%以上的结直肠癌病人中表达缺失。DCC诱导的细胞凋亡是一条新的凋亡通路，不属于已知的两条凋亡通路（线粒体通路和死亡受体通路）。这条新通路在2000年左右被发现，十多年来未有实质性的进展，参与这条通路的蛋白以及其诱导凋亡的机制尚不清楚。本课题组在寻找DCC相互作用蛋白时发现一个蛋白，暂命名为EADIA（Endogenous Antagonist for DCC-Induced Apoptosis），即内源性的DCC诱导凋亡的拮抗剂。我们发现，EADIA直接与DCC结合，并可以显著抑制DCC诱导的细胞凋亡。我们提出一个EADIA调控DCC诱导凋亡的分子机制，此机制可以解释这条新通路如何被激活，这对于揭示DCC诱导细胞凋亡的机制是一个重大进展，可以帮助我们理解结直肠癌的发病机理，并对其治疗提供新的思路（如尝试在DCC缺失的病人中激活DCC下游通路，从而达到治疗的目的）。

中文关键词： C08_结；直肠肿瘤；细胞凋亡；DCC；新通路；分子机制

英文摘要： DCC is a tumor supressor gene which is deleted in more than 70% colorectal cancer patients. Different from the two known apoptosis pathways (mitochondria and death receptor), DCC-induced apoptosis is a new third apoptosis pathway. Since the identification of this new pathway around 2000, little breakthrough has been achieved and little is known about the mechanism or the proteins involed in this pathway. We have found a protein while looking for the DCC-interacting proteins, and we named it EADIA (Endogenous Antagonist for DCC-Induced Apoptosis). We find that EADIA can directly interact with DCC and significantly decrease the apoptosis induced by DCC. Therefore we propose a molecular mechanism of EADIA regulating DCC-induced apoptosis, which could elucidate how this pathway be activated. This will be a significant breakthrough for the mechanism of DCC-induced apoptosis, which may help understanding the pathogenesis of colorectal cancer and provide new ideas for its therapy (for example, we may try to activate the downstream pathway of DCC-induced apoptosis in the DCC-deleted patients).

英文关键词： colorectal cancer;apoptosis;DCC;new pathway;molecular mechanism