肾透明细胞癌易转移、预后差，然而其肿瘤进展的分子机制尚不清楚。本课题组前期通过基因表达谱分析发现，蛋白激酶SRPK1在进展型肾透明细胞癌中高表达；敲低SRPK1抑制肾透明细胞癌生长和转移；共沉淀联合蛋白质谱检测发现，SRPK1结合转录因子CREB1，且影响其新位点（Ser129）磷酸化。因此，我们推测SRPK1通过磷酸化CREB1新位点（Ser129）促进肾透明细胞癌转移。本项目拟：1）探讨CREB1促转移作用对其新位点（Ser129）磷酸化修饰的依赖性；2）探索SRPK1磷酸化CREB1新位点（Ser129）调控其转录活性的具体分子机制；3）探究SRPK1通过磷酸化CREB1新位点（Ser129）促进肾透明细胞癌转移的分子机制，并行靶向干预研究。以此解析SRPK1磷酸化CREB1新位点（Ser129）在肾透明细胞癌转移过程中的关键作用，为肾透明细胞癌的精准治疗提供新靶点。

Patients with clear cell renal cell carcinoma (ccRCC) are prone to metastasis and have a poor prognosis. However, the molecular mechanism of ccRCC progression is unclear. Our team's previous work found that protein kinase SRPK1 is highly expressed in progressive ccRCC by gene expression profile; knockdown of SRPK1 inhibited growth and metastasis of ccRCC; Co-precipitation coupled with protein profiling revealed that SRPK1 binds to the transcription factor CREB1, and affects its new site (Ser129) phosphorylation. Therefore, we speculate that SRPK1 promotes metastasis of ccRCC by phosphorylating CREB1 new site (Ser129). This project intends to: 1) Detect the dependence of CREB1 promoting metastasis on its new site (Ser129) phosphorylation modification; 2) Explore the specific molecular mechanism of SRPK1 phosphorylation CREB1 new site (Ser129) regulating its transcriptional activity; 3) Investigate the molecular mechanism that SRPK1 promotes ccRCC metastasis through phosphorylation of CREB1 new site (Ser129), and conduct targeted intervention studies. Finally, we will identify the key role of SRPK1 phosphorylating CREB1 new site (Ser129) in ccRCC metastasis and provide a new target for the precise therapy for ccRCC patients.