己糖胺生物合成途径代谢酶与OGT介导的O-GlcNAc修饰在肿瘤中的研究进展

Advances in metabolic enzymes in the hexosamine biosynthetic pathway and OGT-mediated O-GlcNAc modification in tumors

摘要:

细胞代谢异常和能量失调被认为是癌症的重要标志。己糖胺生物合成途径（hexosamine biosynthetic pathway，HBP）在多数肿瘤中异常激活。葡萄糖、脂肪酸、氨基酸和谷氨酰胺等是肿瘤生长的重要营养物质，并作为HBP的底物用于合成尿苷二磷酸N -乙酰氨基葡萄糖胺（uridine diphosphate N-acetylglucosamine，UDP-GlcNAc）。UDP-GlcNAc是蛋白质发生氧连接的氮乙酰葡萄糖胺（O-linked N-acetylglucosamine，O-GlcNAc）修饰的供体底物，其被认为在细胞中扮演着“营养感受器”的角色。近年来，HBP代谢酶在癌症病理生理学中的作用被广泛研究，HBP介导的O-GlcNAc糖基化修饰与癌细胞的增殖、存活和转移密切相关。本文对HBP及其在肿瘤中的重要作用进行了综述，并且讨论了靶向HBP治疗癌症的潜在策略。

Abstract:

Cell metabolic abnormalities and dysregulated energy utilization are important markers of cancer. The hexosamine biosynthetic pathway（HBP） is abnormally activated in most tumors. Glucose，fatty acids，amino acids，and glutamine are vital nutrients for tumor growth and serve as the substrates for the biosynthesis of uridine diphosphate N-acetylglucosamine（UDP-GlcNAc） through HBP. UDP-GlcNAc is a donor substrate for O-linked N-acetylglucosamine modification（O-GlcNAc） of proteins，which acts as a “nutrient-sensor” within cells. In recent years，the role of HBP metabolic enzymes in the pathophysiology of cancer has been extensively investigated. HBP-mediated O-GlcNAc modification is closely related to the proliferation，survival，and metastasis of cancer cells. Here，we review HBP and its important roles in tumors，and discuss the potential strategies of cancer treatment by targeting HBP.