ArticleInternational journal of molecular sciences2017
Hsp90α Mediates BMI1 Expression in Breast Cancer Stem/Progenitor Cells through Facilitating Nuclear Translocation of c-Myc and EZH2.
Article in International journal of molecular sciences, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 32 citations in OpenAlex.
- Observation of PICALM::MLLT10-rearrangement and coincidental EZH2 mutations in a patient with acute myeloid leukemia: A case report and review of the literature.BJC reports · 2025Article
- Profiling of Breast Cancer Stem Cell Types/States Shows the Role of CD44International journal of molecular sciences · 2025Article
- Molecular pathway of anticancer effect of next-generation HSP90 inhibitors XL-888 and Debio0932 in neuroblastoma cell line.Medical oncology (Northwood, London, England) · 2024Article
- The occurrence and development of induced pluripotent stem cells.Frontiers in genetics · 2024Review
- Discovery of IHMT-337 as a potent irreversible EZH2 inhibitor targeting CDK4 transcription for malignancies.Signal transduction and targeted therapy · 2023Article
- HSP90-Dependent Upregulation of EZH2 Promotes Hypoxia/Reoxygenation-Induced Pyroptosis by Inhibiting miR-22 in Endothelial Cells.Journal of inflammation research · 2023Article
- Role of O-GlcNAcylation on cancer stem cells: Connecting nutrient sensing to cell plasticity.Advances in cancer research · 2023Review
- Disulfiram/Copper Suppresses Cancer Stem Cell Activity in Differentiated Thyroid Cancer Cells by Inhibiting BMI1 Expression.International journal of molecular sciences · 2022Article
- Review
- Autologous treatment for ALS with implication for broad neuroprotection.Translational neurodegeneration · 2022Article
- Tumor suppressor lnc-CTSLP4 inhibits EMT and metastasis of gastric cancer by attenuating HNRNPAB-dependent Snail transcription.Molecular therapy. Nucleic acids · 2021Article
- MicroRNA regulation of cancer stem cells in the pathogenesis of breast cancer.Cancer cell international · 2021Review
- Regulation of cancer stem cells in triple negative breast cancer.Cancer drug resistance (Alhambra, Calif.) · 2021Review
- The prognostic significance of BMI1 expression in invasive breast cancer is dependent on its molecular subtypes.Breast cancer research and treatment · 2020Article
- Coexpression Analysis of the EZH2 Gene Using The Cancer Genome Atlas and Oncomine Databases Identifies Coexpressed Genes Involved in Biological Networks in Breast Cancer, Glioblastoma, and Prostate Cancer.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- 17-Aminogeldanamycin Inhibits Constitutive Nuclear Factor-Kappa B (NF-κB) Activity in Patient-Derived Melanoma Cell Lines.International journal of molecular sciences · 2020Article
- Review
- HSP90 Inhibitor Ganetespib (STA-9090) Inhibits Tumor Growth in c-Myc-Dependent Esophageal Squamous Cell Carcinoma.OncoTargets and therapy · 2020Article
- The expression profiles and prognostic values of HSPs family members in Head and neck cancer.Cancer cell international · 2020Article
- Heat shock proteins in cancer stem cell maintenance: A potential therapeutic target?Histology and histopathology · 2020Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heat shock protein 90 (Hsp90) is a molecular chaperone that facilitates the correct folding and functionality of its client protein. Numerous Hsp90-client proteins are involved in cancer development. Thus, Hsp90 inhibitors have potential applications as anti-cancer drugs. We previously discovered that Hsp90α expression increased in breast cancer stem cells (BCSCs), which can initiate tumorigenesis and metastasis and resist treatment. In the present study, we further demonstrated that 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), an inhibitor of Hsp90, could suppress the self-renewal of BCSCs by downregulating B lymphoma Mo-MLV insertion region 1 homolog (BMI1), a polycomb family member with oncogenic activity in breast cancer. Through immunoprecipitation analysis, we found that BMI1 did not interact with Hsp90α and that the downregulation of BMI1 by 17-DMAG was mediated by the inhibition of c-Myc and enhancement of zeste homolog 2 (EZH2) expression. The transcriptional and BMI1 promoter-binding activities of c-Myc in BCSCs were inhibited by 17-DMAG treatment. The overexpression of EZH2 attenuated the inhibitory effect of 17-DMAG on BMI1 and c-Myc expression. Furthermore, Hsp90α could be co-immunoprecipitated with c-Myc and EZH2 and bind to the BMI1 promoter. Treatment with 17-DMAG decreased the nuclear expression of EZH2 and c-Myc but not that of Hsp90α. In conclusion, our data suggested that Hsp90α could positively regulate the self-renewal of BCSCs by facilitating the nuclear translocation of c-Myc and EZH2 to maintain BMI1 expression.
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Registered trials
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