Taken together, these findings suggest that serine-mediated one-carbon metabolism is also key for the metabolic alteration of GBM, especially in the tumor microenvironment of low glutamine, and demonstrate a previously unknown role for MTHFD2 in mediating glutamine-deprived stress by redox maintenance through one-carbon metabolism in GBM cells. This evidence concerns the gene MTHFD2 and glioblastoma.