Vitamin D3 promotes the differentiation of colon carcinoma cells by the induction of E-cadherin and the inhibition of <b>β</b>-catenin signaling

Pálmer, Héctor G.; González‐Sancho, José Manuel; Espada, Jesús; Berciano, Marı́a T.; Puig, Isabel; Baulida, Josep; Quintanilla, Miguel; Cano, Amparo; Herreros, Antonio Garcı́a de; Lafarga, Miguel; Múñoz, Alberto

doi:10.1083/jcb.200102028

Cited by 730 publications

(687 citation statements)

References 85 publications

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“…Together, these data suggest that 1,25(OH) 2 D 3 decreases SPRY2 protein stability and SPRY2 gene transcription, but does not alter SPRY2 RNA stability. 1,25(OH) 2 D 3 does not alter the stability of E-cadherin RNA (Pa´lmer et al, 2001) or protein (Supplementary Figure 3). 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.…”

Section: 25(oh)mentioning

confidence: 90%

“…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.…”

Section: 25(oh)mentioning

confidence: 99%

“…We have reported that 1,25(OH) 2 D 3 inhibits the proliferation and promotes the differentiation of human colon cancer cells by the induction of the adhesion molecule E-cadherin and the antagonism of the Wnt/ b-catenin pathway (Pa´lmer et al, 2001;Aguilera et al, 2007)). A transcriptomic analysis revealed a decrease in the level of SPROUTY-2 (SPRY2) RNA on treatment of SW480-ADH cells with 1,25(OH) 2 D 3 (5.6-fold at 4 h) (Pa´lmer et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2010

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SPROUTY-2 (SPRY2) regulates receptor tyrosine kinase signalling and therefore cell growth and differentiation. In this study, we show that SPRY2 expression in colon cancer cells is inhibited by the active vitamin D metabolite 1a,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) through E-cadherin-dependent and -independent mechanisms. In turn, SPRY2 represses both basal and 1,25(OH) 2 D 3 -induced E-cadherin expression. In line with this, SPRY2 induces ZEB1 RNA and protein, but not that of other epithelial-to-mesenchymal transition inducers that repress the CDH1/E-cadherin promoter. Consistently, SPRY2 and E-cadherin protein levels inversely correlate in colon cancer cell lines and xenografted tumours. Moreover, SPRY2 knockdown by small hairpin RNA increases CDH1/E-cadherin expression and, reciprocally, CDH1/E-cadherin knockdown increases that of SPRY2. In colon cancer patients, SPRY2 is upregulated in undifferentiated high-grade tumours and at the invasive front of low-grade carcinomas. Quantification of protein expression in 34 tumours confirmed an inverse correlation between SPRY2 and E-cadherin. Our data demonstrate a tumourigenic action of SPRY2 that is based on the repression of E-cadherin, probably by the induction of ZEB1, and a reciprocal regulation of SPRY2 and E-cadherin that dictates cell phenotype. We propose SPRY2 as a candidate novel marker for high-grade tumours and a target of therapeutic intervention in colon cancer.

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Section: 25(oh)mentioning

confidence: 90%

Section: 25(oh)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2010

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“…The transcription factor ZEB1 also downregulates CDH1 in cultured cells and cooperates with SNAI1 in inducing EMT (Grooteclaes and Frisch, 2000;Guaita et al, 2002;Peinado et al, 2007). In contrast, vitamin D (1a,25-dihydroxyvitamin D 3 ) induces the expression of CDH1 and an epithelial phenotype in human colon cells expressing vitamin D receptor (VDR) (Palmer et al, 2001). In addition, we showed that SNAI1 represses VDR expression in tumor cell lines and that its gene expression in human tumors is associated with CDH1 and VDR downregulation (Palmer et al, 2004;Pena et al, 2005).…”

Section: Introductionmentioning

confidence: 92%

SNAI1 expression in colon cancer related with CDH1 and VDR downregulation in normal adjacent tissue

et al. 2009

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SNAI1, ZEB1, E-cadherin (CDH1), and vitamin D receptor (VDR) genes regulate the epithelial-mesenchymal transition (EMT) that initiates the invasion process of many tumor cells. We hypothesized that this process could also affect the behavior of normal cells adjacent to the tumor. To verify this hypothesis, the expression level of these genes was determined by quantitative RT-PCR in tumor, normal adjacent, and normal distant tissues from 32 colorectal cancer (CC) patients. In addition, we extended the study to human HaCaT normal keratinocytes and SW480-ADH colon cancer cells co-cultured with SW480-ADH cells overexpressing the mouse Snai1 gene. Of 18 CC cases with SNAI1 expression in tumor tissue, five also had SNAI1 in normal adjacent tissue (NAT). Expression of SNAI1 in tumor tissue correlated with downregulation of CDH1 and VDR genes in both tumor (P ¼ 0.047 and P ¼ 0.014, respectively) and NAT lacking SNAI1 expression (P ¼ 0.054 and P ¼ 0.003). ZEB1 expression was directly related to VDR expression in tumor tissue (r ¼ 0.39; P ¼ 0.027) and inversely to CDH1 in NAT (r ¼ À0.46; P ¼ 0.010). CDH1 and VDR were also downregulated in SW480-ADH and MaCaT cells, respectively, when they were co-cultured with Snai1-expressing cells. Furthermore, cytokine analysis showed differences in the conditioned media obtained from the two cell types. These results indicate that histologically normal tissue adjacent to tumor tissue expressing the EMT-inducing gene SNAI1 shows alterations in the expression of epithelial differentiation genes such as CDH1 and VDR.

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“…Another possible mechanism by which p63g-mediated VDR expression may play a role in cancer could be through regulation of b-catenin pathway (Patturajan et al, 2002). VDR activation has been shown to induce differentiation by inhibition of the b-catenin signaling pathway (Palmer et al, 2001). p63 isoforms containing the transactivation domain induces VDR expression which in turn can induce E-Cadherin that can bind up b-catenin.…”

Section: Identification Of Vitamin D Receptor As a Target Of P63mentioning

confidence: 99%

Identification of vitamin D receptor as a target of p63

2006

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Vitamin D3 promotes the differentiation of colon carcinoma cells by the induction of E-cadherin and the inhibition of β-catenin signaling

Cited by 730 publications

References 85 publications

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

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

SNAI1 expression in colon cancer related with CDH1 and VDR downregulation in normal adjacent tissue

Identification of vitamin D receptor as a target of p63

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