膀胱癌是泌尿系统最常见的肿瘤，目前尚无高效的治疗靶点。本团队在鉴定膀胱癌新靶点时筛选到非受体酪氨酸激酶ACK1在膀胱癌中高表达并对膀胱癌生长有调控功能，但具体作用机制尚不明确。申请人在前期工作中发现果蝇Ack蛋白通过调控转录辅因子Yki的活性促进细胞增殖和组织生长，膀胱癌细胞的初步实验也表明ACK1能够结合YAP（Yki同源物）并调控YAP活性。基于上述工作基础我们推测ACK1通过调控YAP活性促进膀胱癌细胞生长。本项目拟开展：一、利用病理样本结合细胞功能实验研究ACK1通过YAP活性调控膀胱癌生长的功能；二、体外磷酸化实验和质谱分析鉴定ACK1磷酸化YAP的作用位点；三、从亚细胞定位，蛋白稳定性和蛋白相互作用等方面分析ACK1调控YAP活性的分子机制。综合上述实验探讨ACK1作为膀胱癌潜在治疗靶点的可行性。本项目将ACK1与YAP两个癌基因功能关联起来，为膀胱癌的诊断治疗提供新的思路。

Bladder cancer is the most common tumor type in urinary system, which has no effective therapeutic target now. When searching for new potential targets in bladder cancer, our team identified non-receptor tyrosine kinase ACK1 as a bladder cancer regulator and found ACK1 highly expressed in bladder cancer cells. However, how ACK1 regulated bladder cancer cell growth was unkown. In previous work, we found Drosophila Ack promoted cell proliferation and tissue growth via promoting transcription co-activator Yki. Experiments performed in bladder cancer cells also suggested ACK1 bound to YAP (the Yki homologue) and regulated YAP activity. Based on the results above, we suggested that ACK1 promotes bladder cancer growth via promoting YAP activity. In this project we plan to: I, analyse the function of ACK1 promoting bladder cancer growth via regulating YAP activity; II, identify YAP phosphorylation sites induced by ACK1 through in vitro kinase assay and mass spectrum analysis; III, analyse the mechanism of ACK1 regulating YAP activity in respects of YAP subcellular localization, protein stability and protein-protein interaction. Our project connected the function of ACK1 and YAP together and may bring new strategy for bladder cancer diagnosis and therapy.