E-cadherin and vitamin D receptor regulation by SNAIL and ZEB1 in colon cancer: clinicopathological correlations

Peña, Cristina; García, José M.; Silva, Javier; Garcı́a, Vanesa; Rodríguez, Rafael Gómez; Alonso, Isabel; Millán, Isabel; Salas, Clara; Herreros, Antonio Garcı́a de; Múñoz, Alberto; Bonilla, Félix

doi:10.1093/hmg/ddi366

Cited by 166 publications

(130 citation statements)

References 41 publications

Supporting

Mentioning

119

Contrasting

Order By: Relevance

“…In this context, the results of SNAI1 or ZEB1 deregulation observed in tumor tissue might be influenced by the expression of these genes in non-epithelial cells, masking the expression in epithelial tumor cells. However, similar changes to those observed in the tumors were detected when using epithelial enriched cell populations in an earlier study (Pena et al, 2005). Therefore, we conclude that alterations found in the expression of these genes in the whole tumor samples of this series correspond to carcinoma cells.…”

Section: Adh-gfp Adh-sn Row Column Cytokine Cytokinefull Name Median supporting

confidence: 88%

“…In addition, these two factors may cooperate in CDH1 repression or act on parallel pathways. This hypothesis is supported by our earlier studies with a large series of colorectal carcinoma, in which we found a loss of relation between SNAI1 expression and CDH1 downregulation when ZEB1 expression was high (Pena et al, 2005). In addition, it should be remembered that the ability of ZEB proteins to work as transcriptional repressors or activators can be modulated by acetylation, a process that selectively allows ZEB proteins to EMT genes in normal tissue adjacent to tumor C Peña et al interact with co-repressors or co-activations such as p300 or CtBP (Postigo et al, 2003).…”

Section: Adh-gfp Adh-sn Row Column Cytokine Cytokinefull Name Median supporting

confidence: 86%

“…As for CDH1 expression, we observed in an earlier study that the quantification of CDH1 RNA in the whole biopsy is a good marker of E-cadherin expression and that non-significant intra-tumor differences were found in E-cadherin staining (Pena et al, 2005), in contrast with other authors' findings (Brabletz et al, 2001).…”

Section: Adh-gfp Adh-sn Row Column Cytokine Cytokinefull Name Median mentioning

confidence: 58%

“…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: 93%

See 3 more Smart Citations

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

et al. 2009

View full text Add to dashboard Cite

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.

show abstract

Section: Adh-gfp Adh-sn Row Column Cytokine Cytokinefull Name Median supporting

confidence: 88%

Section: Adh-gfp Adh-sn Row Column Cytokine Cytokinefull Name Median supporting

confidence: 86%

Section: Adh-gfp Adh-sn Row Column Cytokine Cytokinefull Name Median mentioning

confidence: 58%

Section: Introductionmentioning

confidence: 93%

See 2 more Smart Citations

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

et al. 2009

View full text Add to dashboard Cite

show abstract

“…CtBP1 then recruits HDAC1, and perhaps other effectors (e.g., HMT1), to catalyze histone modification and silencing of the VDR gene promoter. Although VDR gene promoter was shown to be regulated by other E2-box binding proteins in non-breast cells [14,15], ours is the first report of the direct involvement of SLUG in the modulation of the expression of VDR gene in human breast cells.…”

Section: In Vivo Binding Of Slug Ctbp1 and Hdac1 Proteins To The Vdrmentioning

confidence: 70%

In vivo binding to and functional repression of the VDR gene promoter by SLUG in human breast cells

Mittal

Myers

Misra

et al. 2008

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

The regulation of vitamin D receptor (VDR), a key mediator in the vitamin D pathway, in breast cancer etiology has long been of interest. We have shown here that the transcriptional repressor protein SLUG inhibits the expression of VDR in human breast cancer cells. To explore the possibility that SLUG regulates the VDR gene promoter, we cloned a 628 bp fragment (−613 to +15) of the human VDR gene promoter. This region contains three E2-box sequences (CAGGTG/CACCTG), the classical binding site of SLUG. SLUG specifically inhibited VDR gene promoter activity. Chromatin-immunoprecipitation (ChIP) assays revealed that SLUG is recruited on the native VDR gene promoter along with the co-repressor protein CtBP1 and the effector protein HDAC1. These data suggests that SLUG binds to the E2-box sequences of the VDR gene promoter and recruits CtBP1 and HDAC1, which results in the inhibition of VDR gene expression by chromatin remodeling. SLUG is a member of the SNAI family of C 2 H 2 -zinc finger family of transcriptional repressors [4][5][6]. It is involved in the epithelial-mesenchymal transition during development [5], acts as an inhibitor of apoptosis [7], and causes tubulogenesis during breast and kidney developments [4,5]. The genes inhibited by SLUG include E-cadherin [8], claudins [9], BRCA2 [10], and cytokeratins [11]. Our ChIP-DSL analysis of 20,000 human gene promoter array revealed that more than 150 promoters bind to SLUG at their promoters (Mittal, M.K. and Chaudhuri, G., unpublished data). VDR gene is one of the candidate SLUG-regulated genes. Here, we report that SLUG indeed binds in vivo to the VDR gene promoter in human breast cell nucleus and inhibits VDR gene expression by chromatin remodeling.

show abstract

CPP‐E1A fusion peptides inhibit CtBP‐mediated transcriptional repression

Blevins

Zhang

et al. 2018

Molecular Oncology

View full text Add to dashboard Cite

The carboxyl‐terminal binding proteins (CtBP) are transcriptional corepressors that regulate the expression of multiple epithelial‐specific and pro‐apoptotic genes. Overexpression of CtBP occurs in many human cancers where they promote the epithelial‐to‐mesenchymal transition, stem cell‐like features, and cell survival, while knockdown of CtBP in tumor cells results in p53‐independent apoptosis. CtBPs are recruited to their target genes by binding to a conserved PXDLS peptide motif present in multiple DNA‐binding transcription factors. Disrupting the interaction between CtBP and its transcription factor partners may be a means of altering CtBP‐mediated transcriptional repression and a potential approach for cancer therapies. However, small molecules targeting protein–protein interactions have traditionally been difficult to identify. In this study, we took advantage of the fact that CtBP binds to a conserved peptide motif to explore the feasibility of using peptides containing the PXDLS motif fused to cell‐penetrating peptides (CPP) to inhibit CtBP function. We demonstrate that these peptides disrupt the ability of CtBP to interact with its protein partner, E1A, in an AlphaScreen assay. Moreover, these peptides can enter both lung carcinoma and melanoma cells, disrupt the interaction between CtBP and a transcription factor partner, and inhibit CtBP‐mediated transcriptional repression. Finally, the constitutive expression of one such peptide, Pep1‐E1A‐WT, in a melanoma cell line reverses CtBP‐mediated oncogenic phenotypes including proliferation, migration, and sphere formation and limits tumor growth in vivo. Together, our results suggest that CPP‐fused PXDLS‐containing peptides can potentially be developed into a research tool or therapeutic agent targeting CtBP‐mediated transcriptional events in various biological pathways.

show abstract

E-cadherin and vitamin D receptor regulation by SNAIL and ZEB1 in colon cancer: clinicopathological correlations

Cited by 166 publications

References 41 publications

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

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

In vivo binding to and functional repression of the VDR gene promoter by SLUG in human breast cells

CPP‐E1A fusion peptides inhibit CtBP‐mediated transcriptional repression

Contact Info

Product

Resources

About