非浸润性膀胱癌进展为浸润性癌的机制尚不明确，证据表明核转运受体中的输入蛋白（importin）与肿瘤进展关系密切。前期外显子组测序发现浸润性膀胱癌基底肿瘤相对其浅表肿瘤IPO11拷贝数扩增，细胞和免疫组化实验证实IPO11mRNA和其编码蛋白importin11在浸润性癌中高表达，并且IPO11拷贝数与蛋白表达水平有正相关趋势，沉默IPO11可以抑制膀胱癌细胞的迁移和侵袭能力，并且显著下调THBS1表达。由此提出假设：IPO11拷贝数扩增引起IPO11过表达，直接或间接使能够上调THBS1的转录因子在核内异常分布，诱导膀胱癌进展。本项目拟采用免疫共沉淀，质谱分析，ChIP，RNA干扰等技术，通过细胞生物学功能检测，生物信息学分析等方法阐释IPO11过表达上调THBS1的可能分子机制，探讨IPO11在其中发挥的作用，寻找可能的靶蛋白，为膀胱癌进展标志物及靶向药物的筛选提供理论和实践基础。

The molecular mechanism of bladder urothelial carcinoma progression remains unclear. Importins, members of the karyopherin family, are a type of protein that transports cargo protein into the nucleus. Importins have been proven to be associated with the progression of various cancers. We have previously detected the DNA copy number amplification of IPO11 in basal tumors compared with their corresponding superficial tumors through whole exome sequencing in invasive bladder urothelial carcinoma. Further cytological experiments and immunohistochemical study have shown the overexpression of IPO11 mRNA and importin11 encoded by IPO11 in invasive bladder urothelial cancer. This overexpression is positively correlated with increased IPO11 copy number. IPO11 knockdown by RNAi technique inhibits the mobility and invasion of bladder cancer cell and downregulates THBS1 expression. Thus, in this work, we proposed a new molecular mechanism of progression in bladder urothelial cancer. In this mechanism, the overexpression of IPO11 induced by IPO11 DNA copy number amplification contributes to bladder urothelial carcinoma progression through the upregulation of transcription factor for THBS1. To disclose molecular mechanisms of bladder cancer invasion and progression induced by IPO11, we utilized technologies such as co-immunoprecipitation, ChIP, and RNAi to investigate the inter-reaction mechanism between IPO11 and its specific cargos and potential transcription factor binding sites on THBS1 gene through various methods, including cell biological function experiments and bioinformatics analysis. The aim of our study was to clarify the intra-nuclear mechanism of the IPO11 import signaling pathway and thus provide a new strategy for the prediction and target treatment of invasive bladder cancer.