逆转胃癌中高表达YAP促增殖作用的研究

项目名称： 逆转胃癌中高表达YAP促增殖作用的研究

项目编号： No.81201943

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： 许志朋

作者单位： 浙江大学

项目金额： 23万元

中文摘要： YAP(yes-associated protein)为Hippo通路下游的信号转导分子，参与机体多条信号转导通路的调节，包括细胞增殖与凋亡的调控，我们在前期的实验中发现，胃癌中存在着YAP的高表达，应用SiRNA介导YAP基因沉默可明显抑制胃癌细胞的增殖并诱导细胞凋亡，我们认为YAP的高表达促进胃癌细胞的增殖，参与胃癌的发生与发展；然而研究表明，YAP同时具有促进增殖及诱导凋亡的双重作用，在胃癌中，YAP表现为促增殖作用，但其诱导凋亡缺失的机制以及是否具有潜在的促凋亡作用未见文献报道；研究拟以PML为切入点，探讨胃癌中YAP诱导凋亡缺失的机制，并试图逆转高表达YAP促细胞增殖作用，使其转化为诱导细胞凋亡，并进一步阐述胃癌的发生机制以及YAP做为胃癌基因治疗靶点的可能性。

中文关键词： 胃癌；PML；YAP；增殖；

英文摘要： YAP(Yes-associated protein) was a downstream signal transducer of Hippo pathway,and was reported to be implicated in the regulation of several signal pathways,including cell proliferation and apoptosis;In our previous studies, we found an overexpression of YAP in gastric cancer,moreover,YAP gene silencing mediated by SiRNA inhibited proliferation and induced apoptosis in gastric cancer cell line,we suggested that overexpression of YAP might promote cell proliferation and play multiple roles in the pathogenesis of gastric cancer; However,YAP has been reported to have dual effects in the regulation of cell proliferation and apoptosis,it promoted cell proliferation as well as induced cell apoptosis;YAP exhibited an proliferating effect in gastric cancer,while the mechanism of loss of apoptotic effect and whether YAP had a proapoptotic effect in gastric cancer were unknown.Our studies would take PML as a starting point,probing into the mechanisms led to the loss of apoptotic effect of YAP in gastric cancer,trying to reverse the proliferating effect as to induce cell apoptosis,exploring the possibility of YAP as the gene therapy target for gastric cancer.

英文关键词： gastric cancer；PML；YAP；proliferation；