谷氨酰胺酶与肿瘤的关系研究进展

Research progress on relationship between glutaminase and tumor

谷氨酰胺依赖是肿瘤细胞的重要代谢特点,谷氨酰胺酶(GLS)催化谷氨酰胺生成谷氨酸的反应,是谷氨酰胺酵解的第一个代谢酶.GLS可分为肾型谷氨酰胺酶(GLS1)和肝型谷氨酰胺酶(GLS2).大多数肿瘤中GLS1高表达,GLS2低表达.GLS1具有"促癌效应",而GLS2具有"抗癌效应".GLS在多种肿瘤的发生发展过程中起重要作用.GLS对肿瘤的诊断、进展及预后评估均具有十分重要的意义.GLS1是肿瘤代谢治疗的潜在靶点,其特异性抑制剂有望成为新型的抗肿瘤代谢药物.本文综述了GLS的基础和临床研究进展,并着重阐述了GLS在临床诊疗中的应用价值.

Glutamine addiction is one of the metabolic hallmarks of tumor cells. Glutaminase （GLS） catalyzes the first step of glutaminolysis by converting glutamine to glutamate and ammonia. There are two isozymes of GLS, a kidney-type glutaminase （GLS1） and a liver-type glutaminase （GLS2）. GLS1 is upregu- lated in most tumor tissues, while GLS2 is downregulated. GLS1 functions as a tumor-promotor, while GLS2 acts as a tumor-suppressor. GLS plays an important role in the development and progression of multiple tumors. GLS is of much clinical significance in the diagnosis and prognosis evaluation of tumor. GLSI is a potentially important target for cancer metabolic therapeutics, and the specific inhibitors of GLS1 are promising to become the novel anti-cancer drugs. This review summarized the progress of the basic and clinical research of GLS, and focused on the evaluation of the potential value of glutaminase in the clinical diagnosis and treatment.