The Multiple Roles of Glucose-6-Phosphate Dehydrogenase in Tumorigenesis and Cancer Chemoresistance

Life

Shuai Zhang¹  Changliang Shan²  Huanran Sun²  Jiaqi Song² 

[1] School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China;State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China;

关键词: G6PD;    tumorigenesis;    chemotherapy resistance;    inhibitor;    metabolism;    enzyme;   

DOI  :  10.3390/life12020271

来源: DOAJ

【 摘 要 】

The pentose phosphate pathway (PPP) is a branch from glycolysis that begins from glucose-6-phosphate (G6P) and ends up with fructose-6-phosphate (F6P) and glyceraldehyde-3-phosphate (GADP). Its primary physiological significance is to provide nicotinamide adenine dinucleotide phosphate (NADPH) and nucleotides for vital activities such as reactive oxygen species (ROS) defense and DNA synthesis. Glucose-6-phosphate dehydrogenase (G6PD) is a housekeeping protein with 514 amino acids that is also the rate-limiting enzyme of PPP, catalyzing G6P into 6-phosphogluconolactone (6PGL) and producing the first NADPH of this pathway. Increasing evidence indicates that G6PD is upregulated in diverse cancers, and this dysfunction influences DNA synthesis, DNA repair, cell cycle regulation and redox homeostasis, which provides advantageous conditions for cancer cell growth, epithelial-mesenchymal transition (EMT), invasion, metastasis and chemoresistance. Thus, targeting G6PD by inhibitors has been shown as a promising strategy in treating cancer and reversing chemotherapeutic resistance. In this review, we will summarize the existing knowledge concerning G6PD and discuss its role, regulation and inhibitors in cancer development and chemotherapy resistance.

【 授权许可】

Unknown