AZGP1在肾透明细胞癌发生发展中的作用和机制尚不清楚。我们发现AZGP1在肾透明细胞癌中的表达降低，与肾透明细胞癌的分期、分级以及患者的生存期密切相关，并能抑制VHL失活肾癌细胞系的存活和迁移能力，据此提出AZGP1可能在肾透明细胞癌中协同VHL发挥抑癌作用。本项目拟继续利用体外细胞实验明确AZGP1调控肾癌细胞的功能。随后利用基于Cre-Loxp系统的条件基因敲除技术在小鼠肾上皮细胞中特异性敲除Azgp1和Vhl，综合利用各种生物学技术对小鼠模型进行系统的分析，明确AZGP1协同抑制肾透明细胞癌的功能并初步探索其分子机制。最后，利用TCGA数据库中大规模的人体肾透明细胞癌标本验证肾癌重要信号通路效应分子的改变。上述研究将为明确AZGP1在肾透明细胞癌发生发展中的作用提供重要的体内外证据，为个体化治疗策略研究如靶向治疗提供理论基础，以及提供新的与人类肾癌发生发展过程相似的小鼠模型。

The function and mechanisms of AZGP1 in clear cell renal cell carcinoma (ccRCC) tumorigenesis and development remain elusive. We found that the expression of AZGP1 in human ccRCC was downregulated; and was closely related to the stage and classification of ccRCC and the survival of patients. The overexpression of AZGP1 inhibited the survival and migration of renal cancer cells with the inactivation of VHL. It is suggested that AZGP1 may be a tumor suppressor gene in the kidney. This project intends to determine the function of AZGP1 in regulating renal cancer cells in vitro. Then, we will use the Cre-LoxP system to knockout Azgp1 and Vhl in renal epithelial cells under control of the Ksp-Cre. Through biological methods, we will analyze the phenotypes of gene mutant mice to confirm the tumor suppressor function of AZGP1. Moreover, we will explore the molecular mechanisms of AZGP1 in inhibiting the tumorigenesis and development of ccRCC. Finally, we will validate the signaling-related effectors in the large-scale human ccRCC data from TCGA (The Cancer Genome Atlas) database. The above results will provide new insights for better understanding of the function and mechanisms of AZGP1 in tumorigenesis and development, and new drug targets such as AZGP1 and mouse models for the research of individualized medicine.