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PDLIM2 expression is driven by vitamin D and is involved in the pro-adhesion, and anti-migration and -invasion activity of vitamin D

Oncogene volume 33, pages 1904–1911 (2014)Cite this article

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Abstract

1Alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3], the biologically active form of vitamin D3, is a pleiotropic hormone that exerts its effects on a wide range of tissues, resulting in different biological responses such as anticancer activity. It is the ligand of the vitamin D receptor (VDR), a nuclear receptor with transactivating capacity. We demonstrated in this study that 1,25(OH)2D3 induces PDZ-LIM domain-containing protein 2 (PDLIM2) expression. PDLIM2 is an adaptor molecule that links different components of the cytoskeleton, and was recently shown to be repressed in human breast cancer cells by hypermethylation of regulatory promoter regions, leading to enhanced tumorigenicity. We demonstrated that PDLIM2 was a direct target gene of 1,25(OH)2D3; its upregulation was VDR-dependent and a functional VDRE in the promoter was identified. Moreover, 1,25(OH)2D3 induced demethylation of the PDLIM2 promoter, leading to enhanced transcription. Finally, PDLIM2 was found to be crucial for 1,25(OH)2D3-induced cell adhesion and for mediating the ability of 1,25(OH)2D3 to suppress cancer cell migration and invasion. This study provides mechanistic insights into the anticancer activities of 1,25(OH)2D3 in human breast cancer cells.

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Acknowledgements

We thank Ine Beullens, Mark Van Camp, Suzanne Marcelis and Biauw Keng Tan for excellent technical assistance. This work was supported by grants from the University of Leuven (GOA/04/10), Flanders Research Foundation (FWO G.0587.09 and G.0859.11) and Stichting tegen Kanker (212-2008).

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Authors and Affiliations

  1. Laboratory of Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium

    E Vanoirbeek, G Eelen, L Verlinden, G Carmeliet, C Mathieu, R Bouillon & A Verstuyf

  2. Laboratory of Angiogenesis & Neurovascular link, Vesalius Research Center, VIB/KU Leuven, Leuven, Belgium

    G Eelen

  3. Department of Biochemistry, University College, Cork, Ireland

    R O'Connor

  4. Hillman Cancer Center Research Pavilion, University of Pittsburgh, Pittsburgh, PA, USA

    G Xiao

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  1. E Vanoirbeek
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  2. G Eelen
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  4. G Carmeliet
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Correspondence to A Verstuyf.

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Vanoirbeek, E., Eelen, G., Verlinden, L. et al. PDLIM2 expression is driven by vitamin D and is involved in the pro-adhesion, and anti-migration and -invasion activity of vitamin D. Oncogene 33, 1904–1911 (2014). https://doi.org/10.1038/onc.2013.123

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