ArticleCell death and differentiation2020
Downregulation of FOXO3a by DNMT1 promotes breast cancer stem cell properties and tumorigenesis.
Article in Cell death and differentiation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers.
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Who cites it
118 citing papers in PubMed.
- Microbiota as a modulator of drug response: targeting microbial-drug crosstalk in cancer therapy.Gut microbes · 2026Review
- Feedback loops between DNMT1 and autophagy as well as senescence promotes organ aging and canities.Autophagy · 2026Article
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- hsa_circ_0008758 Activates the MDM2/FOXO3a/PGK1 Pathway Through the miR-361-3p/SPIN1 Axis to Promote the Warburg Effect of Non-Small Cell Lung Cancer.Tissue engineering and regenerative medicine · 2026Article
- Role of microRNAs in cisplatin response of cancer stem cells.Stem cell research & therapy · 2026Review
- Chronic psychological stress disrupts liver homeostasis by dysregulating oxidative phosphorylation via the PI3K/AKT/FoxO3a axis.iScience · 2026Article
- Single-cell transcriptome analysis reveals DNMT1Journal of translational medicine · 2026Article
- From Environmental Risk to Cancer Stemness: Epigenetic Regulation in Oral Squamous Cell Carcinoma.Pharmaceuticals (Basel, Switzerland) · 2026Review
- LncRNA TMPO-AS1 aggravates the cisplatin resistance in cervical cancer via miR-140-5p/DNMT1 axis-mediated DNA methylation of KLK10.Medical oncology (Northwood, London, England) · 2026Article
- Article
- Reimagining AHR in Cancer: From Environmental Sensor to Novel Immunomodulatory Therapeutic Target.International journal of biological sciences · 2026Review
- The resilient subset: cancer stem cells at the core of immunotherapy resistance.Immunotherapy advances · 2026Review
- Interplay between Epigenetic and Transcription Factors Mediating Drug Resistance via Stem Cells in Breast Cancer.ACS omega · 2025Review
- DNMT1 modulation of RASSF1A methylation enhances breast cancer brain metastasis.Cell death & disease · 2025Article
- Review
- CENPU promotes tumorigenesis and stem cell properties in triple‑negative breast cancer by suppressing lysosomal furin degradation.International journal of molecular medicine · 2025Article
- Identification of 5mC regulatory factors mediating methylation patterns and prognosis models in head and neck squamous cell carcinoma.Discover oncology · 2025Article
- p38 Regulates FoxO3a-Mediated SOD2 Expression to Prevent Cd-Induced Oxidative Stress in Neuronal Cells.International journal of molecular sciences · 2025Article
- DNMT1 promotes bladder cancer progression and immune escape by inhibiting MYH11 expression by methylating its promoter.International urology and nephrology · 2025Article
- Identification of methylation-related genes and the potential regulatory mechanism of SLAMF6 in CMS4 colorectal cancer.Clinical epigenetics · 2025Article
58 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors.
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Abstract
Breast cancer stem cells (BCSCs) are tumor initiating cells that can self-renew and are highly tumorigenic and chemoresistant. Therefore, the identification of factors critical for BCSC function is vital for the development of therapies. Here, we report that DNMT1-mediated FOXO3a promoter hypermethylation leads to downregulation of FOXO3a expression in breast cancer. FOXO3a is functionally related to the inhibition of FOXM1/SOX2 signaling and to the consequent suppression of BCSCs properties and tumorigenicity. Moreover, we found that SOX2 directly transactivates DNMT1 expression and thereby alters the methylation landscape, which in turn feedback inhibits FOXO3a expression. Inhibition of DNMT activity suppressed tumor growth via regulation of FOXO3a/FOXM1/SOX2 signaling in breast cancer. Clinically, we observed a significant inverse correlation between FOXO3a and FOXM1/SOX2/DNMT1 expression levels, and loss of FOXO3a expression or increased expression of FOXM1, SOX2, and DNMT1 predicted poor prognosis in breast cancer. Collectively, our findings suggest an important role of the DNMT1/FOXO3a/FOXM1/SOX2 pathway in regulating BCSCs properties, suggesting potential therapeutic targets for breast cancer.
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