本课题组长期从事经典凋亡蛋白FADD的非凋亡新生物学功能研究，近年来相继发现了FADD的多种新生物学功能及其机制，较好诠释了FADD生物学功能的多样性。课题组前期的蛋白质组学研究显示：作为经典死亡蛋白的FADD可能参与肿瘤细胞的上皮-间质转化（EMT）过程，并鉴定出核糖核蛋白hnRNP A2/B1作为FADD的一个新相互作用蛋白；FADD缺失促进EMT的发生，而FADD和hnRNP A2/B1共缺失可以逆转肿瘤细胞EMT表型。这些结果提示FADD对肿瘤细胞具有尚未被认识的重要生物学功能。本项目拟采用FADD和hnRNP A2/B1基因改造的细胞和动物模型，系统地研究FADD/hnRNP A2/B1在EMT中的作用及其机制，拓宽对FADD生物学功能和EMT过程的认识和理解，探索将FADD/hnRNP A2/B1及其调控作为肿瘤转移治疗靶点的可能性，为恶性肿瘤的治疗提供新的分子靶点和治疗策略。

Our research team has been long-timely investigating the non-apoptotic biological functions of classical apoptotic protein FADD. Recently we have found several new biological functions and the underlying mechanisms of FADD protein, which have better interpreted the diversity of FADD biological function. Our previous proteomic studies in A549 lung cancer cells indicate that FADD, as a classical death protein, is most likely involved in the epithelial-mesenchymal transition (EMT) process. Also, we have identified a heterogeneous nuclear ribonucleoprotein hnRNP A2/B1 as a novel partner of FADD. FADD deficiency promotes EMT, while FADD and hnRNP A2/B1 double-knockout can reverse the phenotype of EMT. All these results suggest important biological regulation of FADD on tumor cells and this novel function of FADD is probably not due to its apoptotic or death function. This phenotype and detailed mechanism has not been reported up to now. This proposal will use genetically modified cell and animal models of FADD and hnRNP A2/B1 to systematically investigate the role of FADD/hnRNP A2/B1 in EMT and the related mechanisms. This proposal aims to broaden our understanding and knowledge on the biological functions of FADD and EMT. We will also explore the possibility of FADD/hnRNP A2/B1 and its regulation as therapeutic or intervention target for tumor metastasis, and thus provide novel therapeutic target and approach for treatment of cancer.