USP14 modulates stem-like properties, tumorigenicity, and radiotherapy resistance in glioblastoma stem cells through stabilization of MST4-phosphorylated ALKBH5.

ABSTRACT: Rationale: Glioblastoma (GBM) is the most aggressive type of primary brain cancer and contains self-renewing GBM stem cells (GSCs) that contribute to tumor growth and therapeutic resistance. However, molecular determinants governing therapeutic resistance of GSCs are poorly understood. Methods: We performed genome-wide analysis of deubiquitylating enzymes (DUBs) in patient-derived GSCs and used gene-specific shRNAs to identify an important DUB gene contributing to GSC survival and radioresistance. Subsequently, we employed mass spectrometry and immunoprecipitation to show the interaction between USP14 and ALKBH5, and identified the upstream kinase MST4, which is essential for the deubiquitylation and stabilization of ALKBH5. Additionally, we performed integrated transcriptome

SUBMITTER: Zhou X 

PROVIDER: S-EPMC11840735 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature