1α,25-hydroxyvitamin D/VDR suppresses stem-like properties of ovarian cancer cells by restraining nuclear translocation of β-catenin
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View abstract on PubMed
Summary
This summary is machine-generated.1α,25-dihydroxyvitamin D [1α,25(OH)<sub>2</sub>D<sub>3</sub>] inhibits ovarian cancer stem cell properties by reducing sphere formation and tumorigenesis. It also decreases stemness by promoting β-catenin translocation, offering a potential therapeutic target.
Area Of Science
- Oncology
- Molecular Biology
- Endocrinology
Background
- 1α,25-dihydroxyvitamin D [1α,25(OH)<sub>2</sub>D<sub>3</sub>] is known to inhibit cancer cell proliferation and metastasis.
- Its effect on β-catenin translocation in ovarian cancer stem cells (CSCs) is not well understood.
Purpose Of The Study
- To investigate the role of 1α,25(OH)<sub>2</sub>D<sub>3</sub> in suppressing stem-like properties of ovarian CSCs.
- To elucidate the mechanism involving β-catenin translocation.
Main Methods
- Isolation of ovarian CSCs (SP and CD44<sup>+</sup>/CD117<sup>+</sup>) from mouse ovarian surface epithelial (MOSE) cells.
- Assessment of sphere-forming ability, Notch1, Klf levels, and tumorigenesis via limiting dilution assay.
- Analysis of β-catenin translocation, VDR binding, and downstream targets (c-Myc, CyclinD1) in response to 1α,25(OH)<sub>2</sub>D<sub>3</sub> treatment.
Main Results
- 1α,25(OH)<sub>2</sub>D<sub>3</sub> significantly reduced sphere formation, Notch1, and Klf levels in ovarian CSCs.
- 1α,25(OH)<sub>2</sub>D<sub>3</sub> inhibited CSC tumorigenesis in vitro and suppressed stemness in an orthotopic transplantation model.
- 1α,25(OH)<sub>2</sub>D<sub>3</sub> promoted β-catenin translocation from the nucleus to the cytoplasm by binding to VDR, decreasing c-Myc and CyclinD1 levels.
Conclusions
- 1α,25(OH)<sub>2</sub>D<sub>3</sub> effectively inhibits stem-like properties in ovarian cancer cells.
- The mechanism involves restraining nuclear translocation of β-catenin.
- 1α,25(OH)<sub>2</sub>D<sub>3</sub> presents a promising therapeutic target for ovarian cancer treatment.
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