上皮间质转化与肿瘤的转移扩散密切相关。我们过去的研究表明E3泛素连接酶Smurf1介导的小G蛋白RhoA的泛素化降解对于上皮细胞之间的紧密连接的解离是必需的，因而在上皮间质转化的过程中起着重要的作用。本课题的前期工作发现Smurf1还会对形成黏附连接中的重要分子p120-catenin进行单泛素化修饰，使得p120-catenin从黏附连接复合物上解离下来，从而导致黏附连接的解离。我们进一步发现TGFbeta可以诱导Smurf1对p120-catenin的单泛素化修饰。阻止Smurf1介导的p120-catenin单泛素化能够抑制TGFbeta引起的黏附连接的解离。本课题将深入阐明调控Smurf1介导p120-catenin单泛素化修饰的上游信号通路及相关的分子机制，系统地探讨p120-catenin的单泛素化修饰在黏附连接的解离及其上皮间质转移过程中的作用，并考察其对于肿瘤扩散的影响。

Epithelial to mesenchymal transition (EMT) plays an important role in tumor metastasis. Our previous study indicated that E3 ubiquitin ligase Smurf1-mediated degradation of small GTPase RhoA is required for dissociation of tight junctions, therefore acts as a key step in EMT. In our recent study, we found that Smurf1 may also target p120-catenin, a core component of adherens junction complex, for mono-ubiquitination, thereby promoting dissociation of adherens junctions. Moreover, treatment of TGFbeta induces Smurf1-mediated mono-ubiquitination of p120-catenin. Blockade of ubiquitination of p120-catenin mediated by Smurf1 inhibits TGFbeta-induced adherens junction dissociation. In this project, we will scrutinize the signaling pathway(s) and underlying molecular mechanism that regulate Smurf1-mediated mono-ubiquitination of p120-catenin, and systematically examine the role of this mono-ubiquitination of p120-catenin in adherens junction dissociation, EMT, and tumor metastasis.