Fig. 8: c-SRC facilitates glioblastoma progression by remodeling fatty acid synthesis.

Glioma cells exploit glucose and acetate, which permeate the blood-brain barrier, to fulfill their metabolic requirements. Specifically, these cells utilize glucose to generate acetate, releasing a substantial amount of acetate into the extracellular matrix. In glioma, c-SRC is extensively activated and phosphorylates ACSS2 to stimulate the synthesis of cytoplasmic acetyl-CoA from glucose or extracellular matrix-derived acetate. Concurrently, c-SRC-mediated phosphorylation of ACLY inhibits its activity, diverting citrate towards IDH1-catalyze NADPH production, thereby providing reducing equivalents for fatty acid synthesis. Consequently, c-SRC simultaneously satisfies the glioma cell’s need for both acetyl-CoA and NADPH in de novo fatty acid synthesis by coordinately regulating ACSS2 and ACLY, remodeling fatty acid synthesis and fostering the glioblastoma progression. Figure 8 created with BioRender.com released under a Creative Commons Attribution-NonCommerical-NoDerivs 4.0 International license.