Analysis of Snail-1, E-Cadherin and Claudin-1 Expression in Colorectal Adenomas and Carcinomas

Abstract

We report the expression of Snail-1, E-cadherin and claudin-1 by indirect immunohistochemistry in colonic neoplasia. Snail-1 is a zinc finger transcription factor expressed in cells that already have undergone almost complete epithelial-mesenchymal transition (EMT) and have already evaded from the tumor. The main mechanism by which Snail induces EMT is downregulation of E-cadherin, of which expression was shown to be frequently downregulated in many different types of tumors, where it accompanies the invasiveness and metastatic behavior of malignant cells. Moreover, Snail-1 may downregulate the expression of claudin-1, a cell-cell adhesion protein which plays a likely role in progression and dissemination during tumorigenesis. Snail-1 was expressed in both carcinoma and adenoma cells with histologically normal epithelium in the mucosa, adjacent to the tumors, without significant differences, and predominant strong intensity of staining. Statistically significant differences were revealed between normal and tumorous epithelium (p = 0.003) at the subcellular level, where the shift of the protein to the cytoplasm with combined cytoplasmic/nuclear or pure cytoplasmic expression was observed. E-cadherin expression was present in 100% of cases of both adenocarcinomas and adenomas, with prevailing strong membranous immunoreactivity and no differences between protein expression in tumors and normal mucosa. Predominating strong positivity of claudin-1 was detected in tumor cells of adenocarcinomas and adenomas. Marked differences were seen in protein localization, where membranous staining, typical for nontumorous epithelium, changed to combined membranous/cytoplasmic expression in adenocarcinomas (p = 0.0001) and adenomas (0.0002), in which cytoplasmic shift was associated with a higher degree of dysplasia. Furthermore, membranous/cytoplasmic localization was more frequent in the carcinoma group (87%) in comparison with adenomas (51%) (p = 0.0001). We conclude that dystopic subcellular localizations of Snail-1 and claudin-1 may participate in changes of cellular morphology and behavior which might be associated with altered effectory pathways of proteins and thus substantially contribute to the cancer development.

Claudin-3 Overexpression Increases the Malignant Potential of Colorectal Cancer Cells: Roles of ERK1/2 and PI3K-Akt as Modulators of EGFR signaling

“…The EGF-induced changes observed in this study could be attributed to impaired TJ function, which facilitated access to the EGF receptor, EGFR. This receptor is mainly present in the basolateral region and can thus potentially induce neoplastic transformation, as suggested previously [14], [19], [38]. Controversially to our observations, a recent study showed that EGF decreased claudin-3 and -4 via MEK/ERK and/or PI3K/Akt signaling pathways in ovarian cancer cell lines [39].…”

Differential transcription profiles of long non-coding RNAs in primary human brain microvascular endothelial cells in response to meningitic Escherichia coli

“…It is well known that tight junction expression is regulated by many factors4142, but whether lncRNAs are directly involved in this regulation has remained unclear. However, in our correlation results, lnc-TAF9-1 and occludin mRNA were shown to potentially be associated with tight junction regulation (Supplemental Table 6), and our previous data indicate that meningitic E. coli induction of VEGFA and Snail-1 downregulated the expression of tight junctions28.…”

TMPRSS4 correlates with colorectal cancer pathological stage and regulates cell proliferation and self-renewal ability

“…Snail could directly modulate claudin-1 expression 31 and its dystopic subcellular localizations with claudin-1 helped to form cellular morphology. 32 Hence, a new regulation pathway composed of cAbl/ERK/claudin-1/snail as the downstream of TMPRSS4 in EMT regulation of colon cancer cell deserves in-depth investigation. Additionally, EMT program has been suggested to generate cells with features of CSCs 33,34 and we found that by inhibiting TMPRSS4, possibly suppressing EMT, the self-renewal ability of HCT116 could be reduced as reflected by clonogenic formation assays and CSC markers.…”