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

作     者：Qiwei Jiang Yong Li Songwang Cai Xingyuan Shi Yang Yang Zihao Xing Zhenjie He Shengte Wang Yubin Su Meiwan Chen Zhesheng Chen Zhi Shi 

作者机构：Department of Cell Biology&Institute of BiomedicineNational Engineering Research Center of Genetic MedicineState Key Laboratory of Bioactive Molecules and Druggability AssessmentMOE Key Laboratory of Tumor Molecular BiologyGuangdong Provincial Key Laboratory of Bioengineering MedicineCollege of Life Science and TechnologyJinan UniversityGuangzhou 510632China Department of Gastrointestinal Surgery&General Surgerythe Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510080China Department of Thoracic SurgeryThe First Affiliated Hospital of Jinan UniversityGuangzhou 510632China Department of Radiation OncologyThe Fifth Hospital of Guangzhou Medical UniversityGuangzhou 510150China State Key Laboratory of Quality Research in Chinese MedicineInstitute of Chinese Medical SciencesUniversity of MacaoMacao 519000China Department of Pharmaceutical SciencesCollege of Pharmacy and Health SciencesSt.John’s UniversityQueensNY 11439USA 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2024年第14卷第2期

页      面：698-711页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学] 

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) 

主　　题：Gastric cancer GLUL N-Cadherin β-Catenin Enzyme 

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.