Glutamine Synthetase

Glutamine Synthase (GS) is a metabolic enzyme that can catalyze the synthesis of glutamine from ammonia and glutamate, which plays a crucial role in ammonia detoxification, nitrogen balance, and pH regulation. GS is an important diagnostic biomarker for hepatocellular carcinoma, and it is closely involved in tumor development and drug resistance. The glutamine produced by GS catalysis can not only meet the needs of cancer cells for carbonic acid and nitrogen source, but also ensure survival by clearing reactive oxygen species, stimulate proliferation by activating mTOR and Wnt/β-catenin pathways, and mediate immune escape by weakening cytotoxic T cell function and promoting M2 tumor associated macrophage production, Meanwhile, GS can up-regulate ATP binding transporter expression and maintain tumor stem cell phenotype to trigger drug resistance. In lung cancer, renal cancer, colorectal cancer, pancreatic cancer and breast cancer, patients with high GS expression also have shorter survival period and worse prognosis. But GS expression is reduced in gastric cancer, speculated that the tumor can ingest glutamine from the outside without the need for self-synthesis.