Abstract
Several non-hypercalcemic analogs of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) show antitumor activity in a subset of cancer patients. High vitamin D receptor (VDR) expression, which is associated with good prognosis but is lost during tumor progression. We show that the SNAIL transcription factor represses VDR gene expression in human colon cancer cells and blocks the antitumor action of EB1089, a 1,25(OH)2D3 analog, in xenografted mice. In human colon cancers, elevated SNAIL expression correlates with downregulation of VDR.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Hansen, C.M., Binderup, L., Hamberg, K.J. & Carlberg, C. Front. Biosci. 6, D820–D848 (2001).
Lamprecht, S.A. & Lipkin, M. Nat. Rev. Cancer 3, 601–614 (2003).
Dalhoff, K. et al. Br. J. Cancer 89, 252–257 (2003).
Kállay, E. et al. Food Chem. Toxicol. 40, 1191–1196 (2002).
Jurutka, P.W. et al. Rev. Endocr. Metab. Disord. 2, 203–216 (2001).
Cross, H.S. et al. Anticancer Res. 16, 2333–2338 (1996).
Pálmer, H.G. et al. J. Cell Biol. 154, 369–388 (2001).
Cano, A. et al. Nat. Cell Biol. 2, 76–83 (2000).
Batlle, E. et al. Nat. Cell Biol. 2, 84–89 (2000).
Nieto, M.A. Nat. Rev. Mol. Cell Biol. 3, 155–166 (2002).
Pálmer, H.G. et al. Cancer Res. 63, 7799–7806 (2003).
Van de Wetering, M. et al. Cell 111, 241–250 (2002).
Zinser, G.M., Sundberg, J.P. & Welsh, J. Carcinogenesis 23, 2103–2109 (2002).
Makishima, M. et al. Science 296, 1313–1316 (2002).
Huerta, S. et al. Cancer Res. 62, 741–746 (2002).
Acknowledgements
We thank L. Binderup for 1,25(OH)2D3 and EB1089, T. González for calcemia measurement and R. Rycroft for his help with the English manuscript. This study was supported by grants from Fundación Científica de la Asociación Española contra el Cáncer, Ministerio de Ciencia y Tecnología (SAF01-2291) and Instituto de Salud Carlos III (FIS03-C03/10) of Spain.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Supplementary information
Supplementary Fig. 1
Sequence of the human VDR gene promoter. (PDF 102 kb)
Supplementary Fig. 2
Specificity of the repressive effective of SNAIL on human VDR gene promoter. (PDF 162 kb)
Supplementary Fig. 3
High SNAIL levels associate with E-cadherin repression in human colon cancer. (PDF 139 kb)
Supplementary Table 1
Inverse correlation between SNAIL and VDR expression in colon cancer. (PDF 179 kb)
Supplementary Table 2
Statistical analysis of the inverse relation between tumoral SNAIL RNA overexpression and the repression of VDR and E-cadherin expression. (PDF 85 kb)
Rights and permissions
About this article
Cite this article
Pálmer, H., Larriba, M., García, J. et al. The transcription factor SNAIL represses vitamin D receptor expression and responsiveness in human colon cancer. Nat Med 10, 917–919 (2004). https://doi.org/10.1038/nm1095
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nm1095
- Springer Nature America, Inc.
This article is cited by
-
Role of Interleukins in Inflammation-Mediated Tumor Immune Microenvironment Modulation in Colorectal Cancer Pathogenesis
Digestive Diseases and Sciences (2023)
-
The vitamin D analogue calcipotriol promotes an anti-tumorigenic phenotype of human pancreatic CAFs but reduces T cell mediated immunity
Scientific Reports (2020)
-
Exploring vitamin D metabolism and function in cancer
Experimental & Molecular Medicine (2018)
-
The role of vitamin D in hepatic metastases from colorectal cancer
Clinical and Translational Oncology (2018)
-
Vitamin D and renal outcome: the fourth outcome of CKD-MBD? Oshima Award Address 2015
Clinical and Experimental Nephrology (2018)