表皮生长因子受体异构体EGFRvA对HNRNPF的调控和机制研究

项目名称： 表皮生长因子受体异构体EGFRvA对HNRNPF的调控和机制研究

项目编号： No.81472569

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 李宗海

作者单位： 上海交通大学

项目金额： 80万元

中文摘要： 表皮生长因子受体(EGFR)是一种重要的跨膜受体，在多种恶性肿瘤的发生发展中扮演了关键的角色。虽然EGFR靶向药物已成功用于多种肿瘤治疗,但关于EGFR的功能和机理尚不完全清楚。最近，本课题组首次发现了一种新的EGFR 异构体EGFRvA并证实它具有比EGFR更强的促进肿瘤迁移侵袭能力。由于EGFRvA含有独特的羧基末端，因此它很可能特异性地参与某些蛋白的直接调控。本实验室利用TAP串联亲和纯化与质谱的方法对EGFRvA相互作用蛋白做了筛选并通过免疫共沉淀方法进行验证，最终确定了mRNA调控蛋白HNRNPF可以与EGFRvA发生特异性的相互作用。本项目将在这一基础上深入研究肿瘤中EGFRvA对HNRNPF的调控作用及分子机制，揭示EGFRvA调控的新信号通路及其参与肿瘤发生发展的新作用，从而拓展对EGFR的已有认识，也为肿瘤的EGFR靶向治疗提供新的思路和理论依据。

中文关键词： C15_脑；中枢神经系统肿瘤；EGFRvA；表皮生长因子受体；HNRNPF；调控机制

英文摘要： The epidermal growth factor receptor (EGFR) is an important transmemebrane protein receptor, which has been reported to play important roles in the progression and development of various maligancies. Though EGFR-targeted drugs have been approved for treating various cancer types, the function and mechanism of EGFR are still far from clear. Recently, we identified one new EGFR isoform called EGFRvA. Our study revealed that EGFRvA confered more increased invasiveness to cancer than EGFR. Given that EGFRvA contains a novel sequence at C-terminus, it is likely to directly regulate some proteins.Therefore, tandom affinity purification (TAP), mass spectrometry analysis as well as co-immunoprecipitation were applied to screen the proteins interacting with EGFRvA. Interestingly, HNRNPF, one protein for mRNA regulation, was observed to be able to interact with EGFRvA specifically. On these basis, we are going to further elucidate the regulatory role of EGFRvA on HNRNPF as well as its underlying mechanisms. Through this study, it is possible to uncover new signaling pathways mediated by EGFRvA and discover new EGFRvA functions in tumor progression and development, thereby expanding the current knowledge of EGFR and providing new strategies and theoretical basis for EGFR-targeted cancer therapy.

英文关键词： glioma;EGFRvA;EGFR;HNRNPF;regulatory mechanism