GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progresses of gastric cancer

查看全文 作　　者：Qiwei [1]Jiang;Yong [2]Li;Songwang [3]Cai;Xingyuan [4]Shi;Yang [1]Yang;Zihao [1]Xing;Zhenjie [1]He;Shengte [1]Wang;Yubin [1]Su;Meiwan [5]Chen;Zhesheng [6]Chen;Zhi [1]Shi

机构地区：[1]Department of Cell Biology&Institute of Biomedicine,National Engineering Research Center of Genetic Medicine,State Key Laboratory of Bioactive Molecules and Druggability Assessment,MOE Key Laboratory of Tumor Molecular Biology,Guangdong Provincial Key Laboratory of Bioengineering Medicine,College of Life Science and Technology,Jinan University,Guangzhou 510632,China;[2]Department of Gastrointestinal Surgery&General Surgery,the Guangdong Provincial People’s Hospital,Guangdong Academy of Medical Sciences,Guangzhou 510080,China;[3]Department of Thoracic Surgery,The First Affiliated Hospital of Jinan University,Guangzhou 510632,China;[4]Department of Radiation Oncology,The Fifth Hospital of Guangzhou Medical University,Guangzhou 510150,China;[5]State Key Laboratory of Quality Research in Chinese Medicine,Institute of Chinese Medical Sciences,University of Macao,Macao 519000,China;[6]Department of Pharmaceutical Sciences,College of Pharmacy and Health Sciences,St.John’s University,Queens,NY 11439,USA

出　　处：《Acta Pharmaceutica Sinica B》索引2024年第14卷第2期,共14页

基　　金：supported by funds from the National Key Research and Development Program of China No.2017YFA0505104(Zhi Shi);the National Natural Science Foundation of China Nos.81772540 and 82272996(Zhi Shi);the Science and Technology Program of Guangdong No.2019A050510023(Zhi Shi,China);the Science and Technology Program of Guangzhou No.20220-6010081(Zhi Shi,China). 摘　　要：Glutamate-ammonia ligase(GLUL, also known as glutamine synthetase) is a crucial enzyme that catalyzes ammonium and glutamate into glutamine in the ATP-dependent condensation. Although GLUL plays a critical role in multiple cancers, the expression and function of GLUL in gastric cancer remain unclear. In the present study, we have found that the expression level of GLUL was significantly lower in gastric cancer tissues compared with adjacent normal tissues, and correlated with N stage and TNM stage, and low GLUL expression predicted poor survival for gastric cancer patients. Knockdown of GLUL promoted the growth, migration, invasion and metastasis of gastric cancer cells in vitro and in vivo, and vice versa, which was independent of its enzyme activity. Mechanistically, GLUL competed with β-Catenin to bind to N-Cadherin, increased the stability of N-Cadherin and decreased the stability of β-Catenin by alerting their ubiquitination. Furthermore, there were lower N-Cadherin and higher β-Catenin expression levels in gastric cancer tissues compared with adjacent normal tissues. GLUL protein expression was correlated with that of N-Cadherin, and could be the independent prognostic factor in gastric cancer. Our findings reveal that GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progress of gastric cancer. 关键词：Gastric cancer GLUL N-CADHERIN Β-CATENIN ENZYME

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GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progresses of gastric cancer

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