ArticleScientific reports2019
BRCA1 regulates the cancer stem cell fate of breast cancer cells in the context of hypoxia and histone deacetylase inhibitors.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Unraveling the triad of hypoxia, cancer cell stemness, and drug resistance.Journal of hematology & oncology · 2025Review
- SOSTDC1 Nuclear Translocation Facilitates BTIC Maintenance and CHD1-Mediated HR Repair to Promote Tumor Progression and Olaparib Resistance in TNBC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- From single-cell to spatial transcriptomics: decoding the glioma stem cell niche and its clinical implications.Frontiers in immunology · 2024Article
- BRCA1 the Versatile Defender: Molecular to Environmental Perspectives.International journal of molecular sciences · 2023Review
- Review
- Targeting Cancer Stem Cells as the Key Driver of Carcinogenesis and Therapeutic Resistance.International journal of molecular sciences · 2023Review
- Review
- The Breast Cancer Protooncogenes HER2, BRCA1 and BRCA2 and Their Regulation by the iNOS/NOS2 Axis.Antioxidants (Basel, Switzerland) · 2022Review
- Beyond the Double-Strand Breaks: The Role of DNA Repair Proteins in Cancer Stem-Cell Regulation.Cancers · 2021Review
- Emerging Role of E2F Family in Cancer Stem Cells.Frontiers in oncology · 2021Review
- Plasma Metabolome Signature Indicative ofFrontiers in oncology · 2021Article
- EP300 knockdown reduces cancer stem cell phenotype, tumor growth and metastasis in triple negative breast cancer.BMC cancer · 2020Article
- Cell Reversal From a Differentiated to a Stem-Like State at Cancer Initiation.Frontiers in oncology · 2020Article
- Review
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Authors and funding
3 authors.
Funding
Abstract
Cancer cell stemness is essential for enabling malignant progression and clonal evolution. Cancer cell fate is likely determined by complex mechanisms involving both cell-intrinsic pathways and stress signals from tumor microenvironment. In this study, we examined the role of the tumor suppressor BRCA1 and hypoxia in the regulation of cancer cell stemness using genetically matched breast cancer cell lines. We have found that BRCA1, a multifunctional protein involved in DNA repair and epigenetic regulation, plays a critical role in the regulation of cancer stem cell (CSC)-like characteristics. Reconstitution of BRCA1 resulted in significant decrease of the CSC-like populations in breast cancer cells whereas down-regulation of BRCA1 resulted in significant increase of the CSC-like populations. Furthermore, the BRCA1-reconstituted tumor cells are more sensitive to the histone deacetylase (HDAC) inhibitor-induced loss of stemness than the BRCA1-deficient cells are. Surprisingly, hypoxia preferentially blocks HDAC inhibitor-induced differentiation of the BRCA1-reconstituted breast cancer cells. In light of the increasing numbers of clinical trials involving HDAC inhibitors in human cancers, our observations strongly suggest that the BRCA1 status and tumor hypoxia should be considered as potentially important clinical parameters that may affect the therapeutic efficacy of HDAC inhibitors.
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