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

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 unclea...

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Main Authors: Qiwei Jiang (Author), Yong Li (Author), Songwang Cai (Author), Xingyuan Shi (Author), Yang Yang (Author), Zihao Xing (Author), Zhenjie He (Author), Shengte Wang (Author), Yubin Su (Author), Meiwan Chen (Author), Zhesheng Chen (Author), Zhi Shi (Author)
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Published: Elsevier, 2024-02-01T00:00:00Z.
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042 |a dc 
100 1 0 |a Qiwei Jiang  |e author 
700 1 0 |a Yong Li  |e author 
700 1 0 |a Songwang Cai  |e author 
700 1 0 |a Xingyuan Shi  |e author 
700 1 0 |a Yang Yang  |e author 
700 1 0 |a Zihao Xing  |e author 
700 1 0 |a Zhenjie He  |e author 
700 1 0 |a Shengte Wang  |e author 
700 1 0 |a Yubin Su  |e author 
700 1 0 |a Meiwan Chen  |e author 
700 1 0 |a Zhesheng Chen  |e author 
700 1 0 |a Zhi Shi  |e author 
245 0 0 |a GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progresses of gastric cancer 
260 |b Elsevier,   |c 2024-02-01T00:00:00Z. 
500 |a 2211-3835 
500 |a 10.1016/j.apsb.2023.11.008 
520 |a 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. 
546 |a EN 
690 |a Gastric cancer 
690 |a GLUL 
690 |a N-Cadherin 
690 |a β-Catenin 
690 |a Enzyme 
690 |a Protein-protein interaction 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
655 7 |a article  |2 local 
786 0 |n Acta Pharmaceutica Sinica B, Vol 14, Iss 2, Pp 698-711 (2024) 
787 0 |n http://www.sciencedirect.com/science/article/pii/S2211383523004318 
787 0 |n https://doaj.org/toc/2211-3835 
856 4 1 |u https://doaj.org/article/ad5ca24d1e9e498fa1b7c96486c8f313  |z Connect to this object online.