ATXN3 deubiquitinates ZEB1 and facilitates epithelial-mesenchymal transition in glioblastoma.

ABSTRACT: The activation of epithelial-mesenchymal transition (EMT) promotes glioblastoma (GBM) invasion, thereby enhancing its malignancy. Elucidating the underlying mechanisms that regulate EMT is essential for the development of effective treatments for GBM. In this study, we found that GBM tissues and cells exhibit significantly elevated expression levels of ataxin 3 (ATXN3). Functional experiments demonstrated that ATXN3 promotes the invasion, migration, and tumor growth of GBM cells by activating EMT. Mechanistically, ATXN3 was identified as a bona fide deubiquitinase for ZEB1, a key EMT-inducing transcription factor, in GBM cells. ATXN3 interacts directly with ZEB1, cleaves ubiquitin moieties from conjugated substrates and maintains the stability of ZEB1. Ectopic expression of ZEB1 significan

SUBMITTER: Wei R 

PROVIDER: S-EPMC11885642 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature