@article{10902/1260,
year = {2008},
month = {11},
url = {http://hdl.handle.net/10902/1260},
abstract = {The active vitamin D metabolite 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) 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)(2)D(3) has several nongenomic effects of uncertain relevance. We show that 1,25(OH)(2)D(3) induces a transcription-independent Ca(2+) 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)(2)D(3). RhoA-ROCK and MSK1 are also required for the inhibition of Wnt-beta-catenin pathway and cell proliferation. Thus, the action of 1,25(OH)(2)D(3) 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.},
publisher = {Rockefeller University Press},
publisher = {Journal of Cell Biology. 2008 Nov 17;183(4):697-710},
title = {RhoA-ROCK and p38MAPK-MSK1 mediate vitamin D effects on gene expression, phenotype, and Wnt pathway in colon cancer cells},
author = {Ordóñez Morán, Paloma and Larriba, María Jesús and Pálmer, Héctor G. and Valero, Ruth Ana and Barbáchano, Antonio and Duñach, Mireia and García de Herreros, Antonio and Villalobos, Carlos and Berciano Blanco, María Teresa and Lafarga Coscojuela, Miguel Ángel and Muñoz Terol, Alberto},
}