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

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.