RhoA–ROCK and p38MAPK-MSK1 mediate vitamin D effects on gene expression, phenotype, and Wnt pathway in colon cancer cells

Abstract

Abbreviations used in this paper: 1,25(OH) 2 D 3 , 1,25-dihydroxyvitamin D 3 ; ATF1, activating transcription factor 1; CREB, cAMP response element-binding protein; DKK-1, dickkopf-1; DRB, 5,6-dichlorobenzimidazole riboside; ERK, extracellular signal-regulated kinase; MSK1, mitogen-and stress-activated kinase 1; OCN , osteocalcin ; OPN , osteopontin ; qRT-PCR, quantitative RT-PCR; PRK2, protein-related kinase 2; ROCK, Rho-associated coiled kinase; shRNA, small hairpin RNA; TCF, T cell factor; VDR, vitamin D receptor; WB, Western blotting.The online version of this article contains supplemental material.

A Ca2+-dependent signalling circuit regulates influenza A virus internalization and infection

“…Although growing evidence implicates Ca 2 þ in RhoA signalling [54][55][56] , little has been reported about the factor articulating these two molecules. The activity of small GTPases is regulated by the balance between the activities of GEFs and GTPase-activating proteins.…”

Nuclear receptors: Genomic and non-genomic effects converge

“…37 Importantly, VDR is required for both the activation of the non-genomic pathway and the transcriptional effects in human SW480-ADH colon cancer cells, as VDR knock-down by siRNA abrogated the increase of [Ca 2+ ] cyt , the activation of RhoA, p38MAPK and MSK, and the induction of CDH1/E-cadherin and CYP24 by 1,25(OH) 2 D 3 . 37 37 Estradiol seems to bind directly and activate the same Ca 2+ channel and perhaps to bind GPR30 at the plasma membrane in some mammalian neurons and human breast cancer and embryonal kidney cells. [19][20][21]29 Retinoic acid activates RARα target genes by activating the p38MAPK-MSK pathway in human breast cancer cells and mouse embryonal fibroblasts.…”

“…Thus, our group has identified several components of a rapid, non-genomic signaling pathway that is required for 1,25(OH) 2 D 3 to regulate the transcription of many target genes. 37 At first, 1,25(OH) 2 D 3 increases the cytosolic Ca 2+ concentration ([Ca 2+ ] cyt ) by inducing an influx from the external medium. In line with this, the use of inhibitors suggested that L-type voltage-dependent Ca 2+ channels mediate such influx.…”

SPROUTY-2 and E-cadherin regulate reciprocally and dictate colon cancer cell tumourigenicity

“…We then investigated whether the effect of SPRY2 on cell phenotype could be a consequence of a general blockade of 1,25(OH) 2 D 3 action. To this end, we first analysed the expression of vitamin D receptor (VDR), a member of the nuclear receptor superfamily that mediates all known actions of 1,25(OH) 2 D 3 (Ordo´nez-Mora´n et al, 2008). As reported in many systems, 1,25(OH) 2 D 3 increased VDR protein (Wiese et al, 1992;Pike et al, 2007).…”

“…E-cadherin is the main molecule responsible for intercellular adhesion in epithelia and it is induced by 1,25(OH) 2 D 3 in human colon cancer cells (Pa´lmer et al, 2001;Ordo´nez-Mora´n et al, 2008). We examined whether it could be regulated by SPRY2.…”