肾细胞癌简称肾癌，是泌尿系统常见的恶性肿瘤，全世界每年都会有十万多人死于此病。多项研究表明在肾细胞癌中，尤其是在透明肾细胞癌中，E3连接酶SPOP几乎在百分之百的临床样本中都上调。上调的SPOP通过泛素化蛋白酶体途径降解抑癌因子从而促进肾细胞癌的发生发展。我们早前研究发现从果蝇到哺乳动物， SPOP保守性的都下调抑癌因子Sufu。在透明肾细胞癌临床样本中也检测到Sufu与SPOP的负相关性。所以本项目拟在前期研究基础上，深入探索SPOP下调Sufu的分子机制，并在肾细胞癌细胞模型以及裸鼠移植瘤动物模型中对调控机制进行验证。同时通过检测大量人类肾细胞癌样本中SPOP和Sufu的相关性对这一机制的临床价值做出初步评估，为治疗肾细胞癌提供崭新的思路与可能的靶点。

Renal cell carcinoma (RCC) is a common malignancy in the urinary system. More than one hundred thousand deaths are estimated to occur worldwide each year. Several studies have been reported that the E3 ligase SPOP is highly expressed in RCC specimens, especially in all clear cell RCC specimens. The overexpressed SPOP, which can promote tumorigenesis and development in RCC cells, mediates degradation of tumor suppressor through ubiquitin-proteasome pathway. In a previous study, we identified that SPOP downregulated tumor suppressor Sufu in species ranging from Drosophila to Mammals. Moreover, a negative correlation between Sufu and SPOP was also found in the RCC specimens. Therefore, this project is planned to elaborate the molecular mechanisms of how SPOP downregulates Sufu and whether downregulation of Sufu by SPOP is necessary for tumorigenesis of RCC in mouse model and clinical specimens. These studies will provide a novel strategy for RCC therapy.