Fig. 6: Model of metabolic rewiring in GSCs in response to acidosis stress.
From: Rewiring of purine metabolism in response to acidosis stress in glioma stem cells
In response to acidosis stress, GSCs exhibited increased de novo purine nucleotide biosynthesis pathway, which is under the regulation of glucose-6-phosphate dehydrogenase. The overexpression G6PD/H6PD, supports the metabolic dependency of GSCs on nucleotides by enhancing the pentose phosphate pathway (PPP). In parallel, TCA cycle flux was also increased, lends support for the importance of mitochondrial metabolism in GSCs under acidic conditions. This reprogramming of GSCs metabolism driven by acidosis indicates that targeting G6PD/H6PD may serve as a promising therapeutic target for improved glioblastoma therapeutics.
