PDGF signaling inhibits mitophagy in glioblastoma stem cells through N⁶-methyladenosine.

ABSTRACT: Dysregulated growth factor receptor pathways, RNA modifications, and metabolism each promote tumor heterogeneity. Here, we demonstrate that platelet-derived growth factor (PDGF) signaling induces N⁶-methyladenosine (m⁶A) accumulation in glioblastoma (GBM) stem cells (GSCs) to regulate mitophagy. PDGF ligands stimulate early growth response 1 (EGR1) transcription to induce methyltransferase-like 3 (METTL3) to promote GSC proliferation and self-renewal. Targeting the PDGF-METTL3 axis inhibits mitophagy by regulating m⁶A modification of optineurin (OPTN). Forced OPTN expression phenocopies PDGF inhibition, and OPTN levels portend longer survival of GBM patients; these results suggest a tumor-suppressive role for OPTN. Pharmacologic targeting of METTL3 augments

SUBMITTER: Lv D 

PROVIDER: S-EPMC9239307 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature