癌症中的糖异生作用：磷酸烯醇式丙酮酸羧激酶、果糖-1,6-二磷酸酶和葡萄糖-6-磷酸酶的功能与调控
Gluconeogenesis in Cancer: Function and Regulation of PEPCK, FBPase, and G6Pase.
作者信息
Wang Zhanyu, Dong Chenfang
机构信息
Department of Pathology and Pathophysiology, and Department of Surgical Oncology (Breast Center) of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Zhejiang Key Laboratory for Disease Proteomics, Zhejiang University School of Medicine, Hangzhou 310058, China.
Department of Pathology and Pathophysiology, and Department of Surgical Oncology (Breast Center) of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Zhejiang Key Laboratory for Disease Proteomics, Zhejiang University School of Medicine, Hangzhou 310058, China.
出版信息
Trends Cancer. 2019 Jan;5(1):30-45. doi: 10.1016/j.trecan.2018.11.003. Epub 2018 Dec 20.
Cancer cells display a high rate of glycolysis in the presence of oxygen to promote proliferation. Gluconeogenesis, the reverse pathway of glycolysis, can antagonize aerobic glycolysis in cancer via three key enzymes - phosphoenolpyruvate carboxykinase (PEPCK), fructose-1,6-bisphosphatase (FBPase), and glucose-6-phosphatase (G6Pase). Recent studies have revealed that, in addition to metabolic regulation, these enzymes also play a role in signaling, proliferation, and the cancer stem cell (CSC) tumor phenotype. Multifaceted regulation of PEPCK, FBPase, and G6Pase through transcription, epigenetics, post-translational modification, and enzymatic activity is observed in different cancers. We review here the function and regulation of key gluconeogenic enzymes and new therapeutic opportunities.
癌细胞在有氧条件下表现出较高的糖酵解速率以促进增殖。糖异生作用是糖酵解的逆过程，可通过三种关键酶——磷酸烯醇式丙酮酸羧激酶（PEPCK）、果糖-1,6-二磷酸酶（FBPase）和葡萄糖-6-磷酸酶（G6Pase）来对抗癌症中的有氧糖酵解。最近的研究表明，除了代谢调节外，这些酶在信号传导、增殖以及癌症干细胞（CSC）肿瘤表型中也发挥作用。在不同癌症中观察到通过转录、表观遗传学、翻译后修饰和酶活性对PEPCK、FBPase和G6Pase进行多方面调节。我们在此综述关键糖异生酶的功能和调节以及新的治疗机会。
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