高侵袭性严重影响肺腺癌的预后，其分子机制不明。有研究报道c-Src磷酸化修饰的E-cadherin可被Hakai泛素化降解，介导上皮间质转化（EMT），促进细胞侵袭转移。课题组前期研究发现在肺腺癌中Hakai表达缺失，全新E3泛素化酶RNF43可泛素化降解被c-Src磷酸化的E-cadherin，介导EMT，而RNF43与E-cadherin并无作用结构域。我们推测：肺腺癌中RNF43与其他膜蛋白结合，激活其RING结构域，泛素化降解被c-Src磷酸化的E-cadherin。本课题将应用蛋白及基因芯片在肺腺癌及癌旁组织中探索人类E3泛素化酶及相关分子的表达，结合siRNA library筛查，明确RNF43泛素化降解E-cadherin介导肺腺癌EMT的分子机制，揭示c-Src对E-cadherin的磷酸化与其泛素化的关系，探索EMT对肺腺癌生物学行为的影响，提供肺腺癌EMT新干预靶点。

The aggressiveness of lung adenocarcinoma is ascribed to be a poor prognosticator for overall survival in patients with lung adenocarcinoma. To the date, the mechanism underlying the metastasis of lung adenocarcinoma remains unclear. Epithelial-mesenchymal transition (EMT) is characterized as a prometastatic factor in malignant diseases. Previous study reported that c-Src-phosphorylated E-cadherin was ubiquitinated and degraded by Hakai to facilitate EMT. However, we found that Hakai was surprisingly undetectable in lung adenocarcinomas. Furthermore, it was preliminarily proven that RNF43 expressing in a high level in lung adenocarcinomas ubiquitinated and degraded E-cadherin followed by c-Src-mediated phosphorylation to facilitated EMT phenotype. Accordingly, we hypothesize that a brand-new E3 ubiquitin ligase, RNF43, compensates Hakai loss to decrease E-cadherin in order to facilitate EMT through the interaction with some other membrane protein. We plan to conduct the research on clarify the expression levels of human E3 ubiquitin ligase using protein and gene chip. Then, E3 ubiquitin ligase exclusive for E-cadherin, RNF43, is further confirmed by siRNA library screening. It is likely to disclose a novel molecular mechanisem by which E-cadherin is phosphorylated and ubiquitinated to facilitate EMT and to further investigate the biological role of EMT in lung adenocarcinoma. It is expected to provide a theoretical screen for a novelty anti-EMT target and to shed a ligh on the therapy of lung adenocarcinoma.