CD2AP调节Hippo信号通路的机制探索及在肺癌中的功能研究

肺癌是世界范围内癌症相关性死亡的主要原因，Hippo信号通路在肺癌的发生与发展中起着重要作用。本课题利用BioID方法鉴定出LATS的互作蛋白CD2AP(细胞骨架相关蛋白)。前期结果显示，在肺癌细胞A549中，敲低CD2AP能够抑制Hippo信号通路中LATS和YAP的磷酸化，增强YAP靶基因的转录，并促进细胞骨架F-actin的重排和A549细胞的迁移。基于此，本项目拟利用基因敲除系统和肺癌的小鼠模型来进一步研究CD2AP调控Hippo信号通路的分子机制以及在肺癌发生与发展中的作用，该项目的完成将鉴定出Hippo信号通路的一个新的调节因子，完善胞质骨架和Hippo信号通路之间的传导机制，并阐明其在肺癌的发生与发展中的功能，为肺癌的诊疗提供理论基础和潜在靶点。

Lung cancer is the leading cause of cancer-related death worldwide. Hippo signaling pathway plays an important role in the development of lung cancer. We used the BioID method to identify one cytoskeleton-associated protein CD2AP which can interact with LATS. Previous results showed that knockdown of CD2AP in lung cancer cell A549 inhibited the phosphorylation of LATS and YAP in the Hippo signaling pathway, increased the transcription of YAP target genes and promoted the rearrangement of cytoskeleton and the migration of A549 cells. Based on this, we intends to use the knockout system and lung cancer mouse model to further study the mechanism of CD2AP regulating Hippo signaling pathway and its role in the development of lung cancer. The completion of this project will identify a novel regulator in the Hippo signaling pathway, help to understand the transduction mechanism from cytoskeleton to Hippo pathway, elucidate its function in the progression of lung cancer, and provide a theoretical basis and potential targets for the treatment of lung cancer.