ArticleOncotarget2016
Inhibition of deubiquitinases primes glioblastoma cells to apoptosis in vitro and in vivo.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
32 citing papers in PubMed, 39 citations in OpenAlex.
- Multifunctional nanoplatforms based on RNA interference for glioma treatment.American journal of cancer research · 2025Review
- Ets1 mediates sorafenib resistance by regulating mitochondrial ROS pathway in hepatocellular carcinoma.Cell death & disease · 2022Article
- Methodological Approaches for Assessing Metabolomic Changes in Glioblastomas.Methods in molecular biology (Clifton, N.J.) · 2022Review
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- Article
- Dual metabolic reprogramming by ONC201/TIC10 and 2-Deoxyglucose induces energy depletion and synergistic anti-cancer activity in glioblastoma.British journal of cancer · 2020Article
- Critical Roles of Deubiquitinating Enzymes in the Nervous System and Neurodegenerative Disorders.Molecules and cells · 2020Review
- Article
- Targeting the Ubiquitin System in Glioblastoma.Frontiers in oncology · 2020Review
- Review
- Dominant-negative ATF5 rapidly depletes survivin in tumor cells.Cell death & disease · 2019Article
- Bcl-2/Bcl-xL inhibition predominantly synergistically enhances the anti-neoplastic activity of a low-dose CUSP9 repurposed drug regime against glioblastoma.British journal of pharmacology · 2019Article
- Carboxamide derivatives induce apoptosis in the U251 glioma cell line.Oncology letters · 2019Article
- Combined inhibition of RAC1 and Bcl-2/Bcl-xL synergistically induces glioblastoma cell death through down-regulation of the Usp9X/Mcl-1 axis.Cellular oncology (Dordrecht, Netherlands) · 2019Article
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- USP9X deubiquitinates ALDH1A3 and maintains mesenchymal identity in glioblastoma stem cells.The Journal of clinical investigation · 2019Article
- Deubiquitinating ALDH1A3 key to maintaining the culprit of aggressive brain cancer.The Journal of clinical investigation · 2019Article
- WP1130 Enhances TRAIL-Induced Apoptosis through USP9X-Dependent miR-708-Mediated Downregulation of c-FLIP.Cancers · 2019Article
- WP1130 reveals USP24 as a novel target in T-cell acute lymphoblastic leukemia.Cancer cell international · 2019Article
- Usp9X Regulates Cell Death in Malignant Peripheral Nerve Sheath Tumors.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
It remains a challenge in oncology to identify novel drug regimens to efficiently tackle glioblastoma, the most common primary brain tumor in adults. Here, we target deubiquitinases for glioblastoma therapy by utilizing the small-molecule inhibitor WP1130 which has been characterized as a deubiquitinase inhibitor that interferes with the function of Usp9X. Expression analysis data confirm that Usp9X expression is increased in glioblastoma compared to normal brain tissue indicating its potential as a therapeutic. Consistently, increasing concentrations of WP1130 decrease the cellular viability of established, patient-derived xenograft (PDX) and stem cell-like glioblastoma cells. Specific down-regulation of Usp9X reduces viability in glioblastoma cells mimicking the effects of WP1130. Mechanistically, WP1130 elicits apoptosis and increases activation of caspases. Moreover, WP1130 and siRNAs targeting Usp9X reduce the expression of anti-apoptotic Bcl-2 family members and Inhibitor of Apoptosis Proteins, XIAP and Survivin. Pharmacological and genetic interference with Usp9X efficiently sensitized glioblastoma cells to intrinsic and extrinsic apoptotic stimuli. In addition, single treatment with WP1130 elicited anti-glioma activity in an orthotopic proneural murine model of glioblastoma. Finally, the combination treatment of WP1130 and ABT263 inhibited tumor growth more efficiently than each reagent by its own in vivo without detectable side effects or organ toxicity. Taken together, these results suggest that targeting deubiquitinases for glioma therapy is feasible and effective.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.