ArticleThe Journal of clinical investigation2019
USP9X deubiquitinates ALDH1A3 and maintains mesenchymal identity in glioblastoma stem cells.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed.
- AARS2-SIRT5-Driven DLD K445 Lactylation Promotes Cuproptosis Resistance in Glioblastoma Stem Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Metabolic Reprogramming in Glioblastoma Stem Cells Promotes Radiation Resistance Through a H3K18la/USP30/MBOAT2 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Bioinformatics screening identifies USP9X as a pathogenic gene underlying thyroid and breast cancer comorbidity.Journal of molecular histology · 2026Article
- An epithelial cell fate-driven predictive model for liver metastasis risk in primary colorectal cancer through single-cell and multi-omics integration.Journal of translational medicine · 2026Article
- USP5 in cancer: a therapeutic window into metabolism and drug resistance.Journal of translational medicine · 2026Review
- CMA-mediated USP9X degradation promotes SHH medulloblastoma progression by facilitating SUFU ubiquitination.Clinical and translational medicine · 2026Article
- Pathological role of deubiquitinating enzymes in lung cancer: recent insights and advances.American journal of cancer research · 2026Review
- Review
- USP9X Promotes Hepatocellular Carcinoma Progression via Stabilization of HSP90AA1.Journal of hepatocellular carcinoma · 2026Article
- The multifaceted roles of deubiquitinating enzymes (DUBs) in pancreatic ductal adenocarcinoma.Cell death & disease · 2025Review
- S-palmitoylation of c-MET by CK2α-mediated zDHHC15 phosphorylation drives glioblastoma stem cell tumorigenicity.Neuro-oncology · 2025Article
- Phenotypic variations in glioma stem cells: regulatory mechanisms and implications for therapeutic strategies.Journal of translational medicine · 2025Review
- Article
- HDAC6 and USP9X Control Glutamine Metabolism by Stabilizing GS to Promote Glioblastoma Tumorigenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- USP18 deubiquitinates and stabilizes SOX9 to promote the stemness and malignant progression of glioblastoma.Cell death discovery · 2025Article
- SYT7 accelerates nasopharyngeal carcinoma progression via ALDH1A3-mediated STAT3 signaling activation.Oncogenesis · 2025Article
- USP9X integrates TGF-β and hypoxia signalings to promote ovarian cancer chemoresistance via HIF-2α-maintained stemness.Cell death & disease · 2025Article
- PHGDH activation fuels glioblastoma progression and radioresistance via serine synthesis pathway.Journal of experimental & clinical cancer research : CR · 2025Article
- Sesquiterpene Lactones as Promising Anti-Glioblastoma Drug Candidates Exerting Complex Effects on Glioblastoma Cell Viability and Proneural-Mesenchymal Transition.Biomedicines · 2025Review
- USP9X deubiquitinates TRRAP to promote glioblastoma cell proliferation and migration and M2 macrophage polarization.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
9 more citing papers are in PubMed but not listed here.
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16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mesenchymal (MES) subtype of glioblastoma (GBM) stem cells (GSCs) represents a subpopulation of cancer cells that are notorious for their highly aggressive nature and resistance to conventional therapy. Aldehyde dehydrogenase 1A3 (ALDH1A3) has been recently suggested as a key determinant for the maintenance of MES features of GSCs. However, the mechanisms underpinning aberrant ALDH1A3 expression remain elusive. Here, we identified ubiquitin-specific protease 9X (USP9X) as a bona fide deubiquitinase of ALDH1A3 in MES GSCs. USP9X interacted with, depolyubiquitylated, and stabilized ALDH1A3. Moreover, we showed that FACS-sorted USP9Xhi cells were enriched for MES GSCs with high ALDH1A3 activity and potent tumorigenic capacity. Depletion of USP9X markedly downregulated ALDH1A3, resulting in a loss of self-renewal and tumorigenic capacity of MES GSCs, which could be largely rescued by ectopic expression of ALDH1A3. Furthermore, we demonstrated that the USP9X inhibitor WP1130 induced ALDH1A3 degradation and showed marked therapeutic efficacy in MES GSC-derived orthotopic xenograft models. Additionally, USP9X strongly correlated with ALDH1A3 expression in primary human GBM samples and had a prognostic value for patients with the MES subgroup. Collectively, our findings unveil USP9X as a key deubiquitinase for ALDH1A3 protein stabilization and a potential target for GSC-directed therapy.
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