上皮间质转化（EMT）在肾癌侵袭过程中发挥关键作用，目前关于Notch3信号通路参与肾癌EMT过程的报道甚少。我们前期发现肾癌及转移灶中Notch3表达显著下降；在肾癌细胞中沉默Notch3可促进其增殖侵袭并伴EMT分子标记物改变；Notch抑制剂处理肾癌细胞后发现促进EMT的ARTN上调和转录抑制因子Hes1下调；将Hes1沉默亦可明显上调ARTN。由此我们猜测肾癌中Notch3失活可减弱Hes1对ARTN抑制从而促进EMT发生。本课题将运用组织芯片、Chip-Seq、转录组测序、EMSA、荧光素酶表达实验等多种方法阐明Notch3信号和肾癌EMT的关系；通过强力霉素诱导表达Notch3，用动物活体成像和激光扫描共聚焦技术评估在体水平恢复该信号对晚期肾癌治疗的应用价值。本项目对揭示Notch3失活促进肾癌EMT的分子机制有重要科学意义，为将来制定更合理的个体化诊疗策略提供临床新思路。

Epithelial - mesenchymal transition (EMT) plays a key role in renal caner invasion. So far, there are few reports about the relationship between Notch3 and EMT in renal tumor. In previous work, we firstly detected the low expression of Notch3 both in renal tumor and metastasis via a tissue microarray. Knockdown Notch3 not only promotes cell proliferation and invasion, also with the alteration of series of EMT molecular markers. After Notch inhibition, we found ARTN which can promote EMT increase, when the transcription repressor Hes1 decrease adversely. ARTN can be upregulated by Hes1 knockdown as well. Thus, we proposed a hypothesis that Notch3 inactivation may increase ARTN as the transcription repression ability from Hes1 have been attenuated. This study will utilize tissue microarray, Chip-Seq, transcriptome sequencing, EMSA, luciferase assay, etc to reveal the association between Notch3 and EMT in renal cancer. Furthermore, after inducing Notch3 by doxcyline, in vivo imaging and confocal laser scanning will perform to evaluate the applicative value for recruiting Notch3 in advanced renal cancer mouse model. This project has important scientific significance in revealing the molecular mechanisms for promoting renal cancer EMT by Notch3 inactivation. Besides, it provides clinical novel ideas for making more reasonable individual therapeutic strategies in future.