ArticleThe Journal of steroid biochemistry and molecular biology2015
HES1-mediated inhibition of Notch1 signaling by a Gemini vitamin D analog leads to decreased CD44(+)/CD24(-/low) tumor-initiating subpopulation in basal-like breast cancer.
Article in The Journal of steroid biochemistry and molecular biology, 2015. 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, 49 citations in OpenAlex.
- Review
- Breast Cancer Metastasis: Mechanisms and Therapeutic Implications.International journal of molecular sciences · 2022Review
- Review
- Modulation of Notch Signaling Pathway by Bioactive Dietary Agents.International journal of molecular sciences · 2022Review
- Vitamin D and Breast Cancer: Mechanistic Update.JBMR plus · 2021Article
- Mammary Development and Breast Cancer: a Notch Perspective.Journal of mammary gland biology and neoplasia · 2021Review
- Emerging role of tumor cell plasticity in modifying therapeutic response.Signal transduction and targeted therapy · 2020Review
- Review
- Analysis of the Transcriptome: Regulation of Cancer Stemness in Breast Ductal CarcinomaCancer prevention research (Philadelphia, Pa.) · 2020Article
- Notch and breast cancer metastasis: Current knowledge, new sights and targeted therapy.Oncology letters · 2019Review
- Evaluation of the prognostic significances of γ-secretase genes in pancreatic cancer.Oncology letters · 2019Article
- Bacoside A Induced Sub-G0 Arrest and Early Apoptosis in Human Glioblastoma Cell Line U-87 MG through Notch Signaling Pathway.Brain tumor research and treatment · 2019Article
- Repurposing vitamin D for treatment of human malignanciesActa pharmaceutica Sinica. B · 2019Review
- Article
- Tocopherols inhibit estrogen-induced cancer stemness and OCT4 signaling in breast cancer.Carcinogenesis · 2018Article
- The oncogenic effects of HES1 on salivary adenoid cystic carcinoma cell growth and metastasis.BMC cancer · 2018Article
- Quantum dot-based immunofluorescent imaging and quantitative detection of DNER and prognostic value in prostate cancer.Cancer biomarkers : section A of Disease markers · 2018Article
- Identification of CD24 as a marker for tumorigenesis of melanoma.OncoTargets and therapy · 2018Article
- Novel molecular insights and new therapeutic strategies in osteosarcoma.Cancer cell international · 2018Review
- Lunatic Fringe and p53 Cooperatively Suppress Mesenchymal Stem-Like Breast Cancer.Neoplasia (New York, N.Y.) · 2017Article
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7 authors at 2 institutions in 1 country.
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Abstract
Tumor-initiating cells (also known as cancer stem cells) are the subpopulation of cells shown to be responsible for tumor initiation, maintenance and recurrence. In breast cancer, CD44(+)/CD24(-/low) cells were identified as tumor-initiating cells. We previously reported that a Gemini vitamin D analog, 1,25-dihydroxy-20R-21(3-hydroxy-3-deuteromethyl-4,4,4-trideuterobutyl)-23-yne-26,27-hexafluoro-cholecalciferol (BXL0124), reduced CD44(+)/CD24(-/low) cells in MCF10DCIS basal-like breast cancer cells. Since Notch has been identified as one of the key signaling pathways involved in breast cancer stem cells, the effect of BXL0124 on the Notch signaling pathway was investigated in breast cancer. The CD44(+)/CD24(-/low) subpopulation of MCF10DCIS cells showed elevated Notch1 signaling and increased cell proliferation compared to the CD44(+)/CD24(high) subpopulation. Treatment with the Gemini vitamin D analog BXL0124 decreased the level of activated Notch1 receptor. In addition, mRNA and protein levels of the Notch ligands, Jagged-1, Jagged-2 and DLL1, were significantly reduced by treatment with BXL0124, which was followed by repression of c-Myc, a key downstream target of Notch signaling. Interestingly, HES1, a known downstream target of Notch signaling, was rapidly induced by treatment with BXL0124. The inhibitory effect of BXL0124 on Notch signaling was reversed by knockdown of HES1. Overexpression of HES1 inhibited Notch1 signaling and reduced the CD44(+)/CD24(-/low) subpopulation, confirming a role of HES1 in Notch1 signaling. In conclusion, the Gemini vitamin D analog, BXL0124, represses the tumor-initiating subpopulation by HES1-mediated inhibition of Notch1 signaling. The present study demonstrates BXL0124 as a potent inhibitor of Notch signaling to target tumor-initiating cells in basal-like breast cancer. This article is part of a Special Issue entitled "17th Vitamin D Workshop".
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