EGFR/SRC/ERK-stabilized YTHDF2 promotes cholesterol dysregulation and invasive growth of glioblastoma.

ABSTRACT: Glioblastoma (GBM) is the most common type of adult malignant brain tumor, but its molecular mechanisms are not well understood. In addition, the knowledge of the disease-associated expression and function of YTHDF2 remains very limited. Here, we show that YTHDF2 overexpression clinically correlates with poor glioma patient prognosis. EGFR that is constitutively activated in the majority of GBM causes YTHDF2 overexpression through the EGFR/SRC/ERK pathway. EGFR/SRC/ERK signaling phosphorylates YTHDF2 serine39 and threonine381, thereby stabilizes YTHDF2 protein. YTHDF2 is required for GBM cell proliferation, invasion, and tumorigenesis. YTHDF2 facilitates m⁶A-dependent mRNA decay of LXRA and HIVEP2, which impacts the glioma patient survival. YTHDF2 promotes tumorigenesis of GBM c

SUBMITTER: Fang R 

PROVIDER: S-EPMC7794382 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature