RT info:eu-repo/semantics/article
T1 RhoA–ROCK and p38MAPK-MSK1 mediate vitamin D effects on gene expression, phenotype, and Wnt pathway in colon cancer cells
A1 Ordóñez Morán, Paloma
A1 Larriba, María Jesús
A1 García Palmer, Héctor
A1 Valero, Ruth Ana
A1 Barbáchano Becerril, Antonio
A1 Duñach Masjuan, Mireia
A1 García de Herreros, Antonio
A1 Villalobos Jorge, Carlos
A1 Berciano, María Teresa
A1 Lafarga Coscojuela, Miguel Ángel
A1 Muñoz Terol, Alberto
K1 Colorectal cancer
K1 Cáncer colorrectal
K1 Vitamin D
K1 Vitamina D
K1 Gene expression
K1 Expresión génica
K1 Phenotype
K1 Fenotipo
AB 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.
PB Rockefeller University Press
SN 1540-8140
YR 2008
FD 2008
LK http://uvadoc.uva.es/handle/10324/45078
UL http://uvadoc.uva.es/handle/10324/45078
LA eng
NO Journal of Cell Biology, 2008, vol. 183, n. 4. p. 697-710
NO Producción Científica
DS UVaDOC
RD 26-dic-2024