卵巢癌细胞中血小板活化因子受体与表皮生长因子受体信号通路串话研究

项目名称： 卵巢癌细胞中血小板活化因子受体与表皮生长因子受体信号通路串话研究

项目编号： No.81202052

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： 姜伟

作者单位： 复旦大学

项目金额： 23万元

中文摘要： 血小板活化因子（PAF）在肿瘤中的作用近年来受到关注，而目前卵巢癌中PAF及其受体(PAFR)的研究尚未受重视。我们前期发现PAFR在非粘液性卵巢癌中高表达，PAFR活化后可刺激肿瘤细胞增殖和侵袭；PAF作用肿瘤细胞后，不但可经FAK、Src激活PI3K，Akt，MAPK等与EGFR信号通路直接相关的蛋白；且可引起较弱EGFR磷酸化。为此，我们提出假说，PAF可通过"转活"（transactivation）部分激活EGFR信号通路，且PAFR与EGFR信号通路下游存在串话（cross talk）。为验证这一假说，我们拟采用慢病毒转染、shRNA、免疫共沉淀、Western Blot等手段，从分子、蛋白水平多方面深入探讨PAF/PAFR对卵巢癌细胞作用的相关机制，明确其与EGFR信号通路之间的关系。本研究将从PAF/PAFR这一全新角度补充现有的卵巢癌相关信号通路，为靶向治疗研究提供新思路。

中文关键词： 卵巢癌；血小板活化因子受体；表皮生长因子受体；信号通路；串话

英文摘要： Although the role of platelet-activating factor (PAF) in tumor has been paid more attention in recent years, the function of PAF and its receptor (PAFR) hasn't been valued in ovarian cancer yet. Our previously study demonstrated that PAFR was highly expressed in non-mucinous ovarian cancer cells. The activated PAFR could stimulate cell proliferation and invasion significantly. PAF could activate PI3K, Akt, and MAPK via FAK and Src, and induce a weak phosphorylation of EGFR as well. To this end, we propose the hypothesis, 1) The PAF may partially activate EGFR by transactivation. 2) There is cross talk between the PAFR and EGFR signaling pathway. To test this hypothesis, we would perform such experiments as lentiviral transfection, shRNA, co-immunoprecipitation, Western Blot and others, and explore the relevant mechanisms of PAF/PAFR on ovarian cancer cell. The study would complement the existing ovarian cancer associated signaling pathway from the new perspective of PAF/PAFR, which could provide new ideas for targeted therapy.

英文关键词： ovarian cancer；platelet activating factor receptor；epidermal growth factor receptor；signaling pathway；crosstalk