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    Por favor, use este identificador para citar o enlazar este ítem:http://uvadoc.uva.es/handle/10324/45078

    Título
    RhoA–ROCK and p38MAPK-MSK1 mediate vitamin D effects on gene expression, phenotype, and Wnt pathway in colon cancer cells
    Autor
    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
    Año del Documento
    2008
    Editorial
    Rockefeller University Press
    Descripción
    Producción Científica
    Documento Fuente
    Journal of Cell Biology, 2008, vol. 183, n. 4. p. 697-710
    Abstract
    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.
    Palabras Clave
    Colorectal cancer
    Cáncer colorrectal
    Vitamin D
    Vitamina D
    Gene expression
    Expresión génica
    Phenotype
    Fenotipo
    ISSN
    1540-8140
    Revisión por pares
    SI
    DOI
    10.1083/jcb.200803020
    Patrocinador
    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)
    Version del Editor
    https://rupress.org/jcb/article/183/4/697/45660/RhoA-ROCK-and-p38MAPK-MSK1-mediate-vitamin-D
    Propietario de los Derechos
    © 2008 Rockefeller University Press
    Idioma
    eng
    URI
    http://uvadoc.uva.es/handle/10324/45078
    Tipo de versión
    info:eu-repo/semantics/publishedVersion
    Derechos
    openAccess
    Collections
    • CFC - Artículos de Revista [38]
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    Attribution-NonCommercial-NoDerivs 3.0 UnportedExcept where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 3.0 Unported

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