ArticleOncotarget2015
Combined inhibition of Bcl-2/Bcl-xL and Usp9X/Bag3 overcomes apoptotic resistance in glioblastoma in vitro and in vivo.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 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
34 citing papers in PubMed, 52 citations in OpenAlex.
- Pulsed Electromagnetic Fields Enhance Resveratrol-Induced Apoptosis Through Modulation of Apoptotic Signaling in U87-MG Glioblastoma Cells.International journal of molecular sciences · 2026Article
- CA3 bridges dietary restriction to glioblastoma suppression and tumor progression as a key downstream effector.Scientific reports · 2025Article
- Cellular senescence in malignant cells promotes tumor progression in mouse and patient Glioblastoma.Nature communications · 2023Article
- Bcl-XL but Not Bcl-2 Is a Potential Target in Medulloblastoma Therapy.Pharmaceuticals (Basel, Switzerland) · 2022Article
- The role of BAG3 in health and disease: A "Magic BAG of Tricks".Journal of cellular biochemistry · 2022Review
- Methodological Approaches for Assessing Metabolomic Changes in Glioblastomas.Methods in molecular biology (Clifton, N.J.) · 2022Review
- The Role of ER Stress-Related Phenomena in the Biology of Malignant Peripheral Nerve Sheath Tumors.International journal of molecular sciences · 2021Review
- Article
- redPATH: Reconstructing the Pseudo Development Time of Cell Lineages in Single-cell RNA-seq Data and Applications in Cancer.Genomics, proteomics & bioinformatics · 2021Article
- MicroRNA‑22 regulates autophagy and apoptosis in cisplatin resistance of osteosarcoma.Molecular medicine reports · 2020Article
- Senescence Induced by BMI1 Inhibition Is a Therapeutic Vulnerability in H3K27M-Mutant DIPG.Cell reports · 2020Article
- Epigenetic Targeting of Mcl-1 Is Synthetically Lethal with Bcl-xL/Bcl-2 Inhibition in Model Systems of Glioblastoma.Cancers · 2020Article
- Dual metabolic reprogramming by ONC201/TIC10 and 2-Deoxyglucose induces energy depletion and synergistic anti-cancer activity in glioblastoma.British journal of cancer · 2020Article
- Heat Shock Proteins in Glioblastoma Biology: Where Do We Stand?International journal of molecular sciences · 2019Review
- Drug resistance-related microRNAs in osteosarcoma: Translating basic evidence into therapeutic strategies.Journal of cellular and molecular medicine · 2019Review
- Behaviors of Glioblastoma Cells in in Vitro Microenvironments.Scientific reports · 2019Article
- Usp9X Regulates Cell Death in Malignant Peripheral Nerve Sheath Tumors.Scientific reports · 2018Article
- Metabolic Reprogramming by Dual AKT/ERK Inhibition through Imipridones Elicits Unique Vulnerabilities in Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Inhibition of Bcl-2/Bcl-xL and c-MET causes synthetic lethality in model systems of glioblastoma.Scientific reports · 2018Article
- Analysis of microarrays of miR-34a and its identification of prospective target gene signature in hepatocellular carcinoma.BMC cancer · 2018Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Despite great efforts taken to advance therapeutic measures for patients with glioblastoma, the clinical prognosis remains grim. The antiapoptotic Bcl-2 family protein Mcl-1 is overexpressed in glioblastoma and represents an important resistance factor to the BH-3 mimetic ABT263. In this study, we show that combined treatment with ABT263 and GX15-070 overcomes apoptotic resistance in established glioblastoma cell lines, glioma stem-like cells and primary cultures. Moreover, this treatment regimen also proves to be advantageous in vivo. On the molecular level, GX15-070 enhanced apoptosis by posttranslational down-regulation of the deubiquitinase, Usp9X, and the chaperone Bag3, leading to a sustained depletion of Mcl-1 protein levels. Moreover, knock-down of Usp9X or Bag3 depleted endogenous Mcl-1 protein levels and in turn enhanced apoptosis induced through Bcl-2/Bcl-xL inhibition. In conclusion, combined treatment with ABT263 and GX15-070 results in a significantly enhanced anti-cancer activity in vitro as well as in vivo in the setting of glioblastoma. Both drugs, ABT263 and GX15-070 have been evaluated in clinical studies which facilitates the translational aspect of taking this combinatorial approach to the clinical setting. Furthermore we present a novel mechanism by which GX15-070 counteracts Mcl-1 expression which may lay a foundation for a novel target in cancer therapy.
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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.