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oai:uvadoc.uva.es:10324/450782021-06-24T07:17:13Zcom_10324_44585com_10324_954com_10324_894col_10324_44586

Ordóñez Morán, Paloma Larriba, María Jesús García Palmer, Héctor Valero, Ruth Ana Barbáchano Becerril, Antonio Duñach Masjuan, Mireia García de Herreros, Antonio Villalobos Jorge, Carlos Berciano, María Teresa Lafarga Coscojuela, Miguel Ángel Muñoz Terol, Alberto 2021-01-19T13:31:14Z 2021-01-19T13:31:14Z 2008 Journal of Cell Biology, 2008, vol. 183, n. 4. p. 697-710 1540-8140 http://uvadoc.uva.es/handle/10324/45078 10.1083/jcb.200803020 Producción Científica The active vitamin D metabolite 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) inhibits proliferation and promotes differentiation of colon cancer cells through the activation of vitamin D receptor (VDR), a transcription factor of the nuclear receptor superfamily. Additionally, 1,25(OH)2D3 has several nongenomic effects of uncertain relevance. We show that 1,25(OH)2D3 induces a transcription-independent Ca2+ influx and activation of RhoA–Rho-associated coiled kinase (ROCK). This requires VDR and is followed by activation of the p38 mitogen-activated protein kinase (p38MAPK) and mitogen- and stress-activated kinase 1 (MSK1). As shown by the use of chemical inhibitors, dominant-negative mutants and small interfering RNA, RhoA–ROCK, and p38MAPK-MSK1 activation is necessary for the induction of CDH1/E-cadherin, CYP24, and other genes and of an adhesive phenotype by 1,25(OH)2D3. RhoA–ROCK and MSK1 are also required for the inhibition of Wnt–β-catenin pathway and cell proliferation. Thus, the action of 1,25(OH)2D3 on colon carcinoma cells depends on the dual action of VDR as a transcription factor and a nongenomic activator of RhoA–ROCK and p38MAPK-MSK1. Ministerio de Ciencia, Innovación y Universidades (grant SAF2007-60341) Ministerio de Sanidad, Consumo y Bienestar Social (grant RD06/0020/0009) Comunidad de Madrid (grant S-GEN-0266/2006) Unión Europea (grant MRTN-CT-2005-019496) application/pdf eng Rockefeller University Press info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/3.0/ © 2008 Rockefeller University Press Attribution-NonCommercial-NoDerivs 3.0 Unported Colorectal cancer Cáncer colorrectal Vitamin D Vitamina D Gene expression Expresión génica Phenotype Fenotipo RhoA–ROCK and p38MAPK-MSK1 mediate vitamin D effects on gene expression, phenotype, and Wnt pathway in colon cancer cells info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion https://rupress.org/jcb/article/183/4/697/45660/RhoA-ROCK-and-p38MAPK-MSK1-mediate-vitamin-D SI