MAT2a and AHCY inhibition disrupts antioxidant metabolism and reduces glioblastoma cell survival.

ABSTRACT: Glioblastoma (GBM) is a highly aggressive primary malignant adult brain tumor that inevitably recurs with a fatal prognosis. This is due in part to metabolic reprogramming that allows tumors to evade treatment. We therefore must uncover the pathways mediating these adaptations to develop novel and effective treatments. We searched for genes that are essential in GBM cells as measured by a whole-genome pan-cancer CRISPR screen available from DepMap and identified the methionine metabolism genes MAT2A and AHCY. We conducted genetic knockdown, evaluated mitochondrial respiration, and performed targeted metabolomics to study the function of these genes in GBM. We demonstrate that MAT2A or AHCY knockdown induces oxidative stress, hinders cellular respiration, and red

SUBMITTER: Rowland EC 

PROVIDER: S-EPMC11601785 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature