上皮间质转化（EMT)）是胃癌发生侵袭转移导致患者死亡的重要原因。申请人前期研究发现谷氨酸胺连接酶（GLUL）在胃癌组织中表达明显低于癌旁组织，并与患者预后密切相关。在胃癌细胞中敲低GLUL引起EMT变化使细胞增殖、迁移和侵袭能力显著增强，而恢复GLUL表达可逆转这些变化。随后发现GLUL可能通过与N-Cadherin蛋白相互结合，抑制N-Cadherin与β-Catenin蛋白的结合，引起β-Catenin蛋白降解，抑制EMT，但其确切的作用和机制还不清楚。本项目将采用一系列实验方法和技术，结合胃癌患者临床病理和预后随访数据，在分子、细胞和动物水平上深入系统地研究GLUL结合N-Cadherin蛋白抑制胃癌EMT的作用和机制，这将为揭示GLUL和N-Cadherin的生物学特性及功能提供重要的补充，也将为阐明胃癌EMT的机制提供重要的理论依据，有助于探索并开发新的胃癌治疗靶点和诊疗策略。

Epithelial-mesenchymal transition (EMT) initiates the invasion and metastasis in gastric cancer, which is the main death reason of patients with gastric cancer. Our preliminary work has shown that the protein levels of glutamate-ammonia ligase (GLUL) is significantly lower in gastric cancer cell lines and tissues compared with normal gastric cell lines and adjacent tissues, and correlated with prognosis. Knockdown of GLUL induces EMT and promotes the growth, migration and invasion of gastric cancer cells, and these are reversed by restoration of GLUL expression. Moreover, GLUL can bind with N-Cadherin, interupt the interaction of N-Cadherin and β-Catenin, promote β-Catenin degradation, and suppress EMT. However, the function and mechanism of GLUL binding with N-Cadherin to inhibit EMT in gastric cancer is still unclear. This project will use a series of methods and technologies as well as clinical data to address these issues at the molecular, cellular and animal levels. It will be a rich complement to understand the biological characteristics and functions of GLUL and N-Cadherin, provide the important clue to know the mechanism of EMT, and also contribute to the development of new targets and strategies of therapy as well as diagnosis in gastric cancer.