E-cadherin and β-catenin adhesion proteins correlate positively with connexins in colorectal cancer

Abstract

The majority of solid cancers present with qualitative and quantitative aberrations of adhesion proteins, including E-cadherin and β-catenin, and connexin (Cx) gap junction proteins, which is consistent with alterations in the expression and location of such proteins in neoplastic cells. Since there are no data on the correlation between adhesion proteins and Cxs in human colorectal cancer (CRC), the aim of the present study was to evaluate the expression and correlation between these proteins. Tissue specimens were obtained from 151 cases of surgically removed colorectal adenocarcinomas. The samples were examined by immunohistochemistry with the use of antibodies against E-cadherin, β-catenin and the three Cxs: Cx26, Cx32 and Cx43. The aberrant expression of the studied adhesion proteins (primarily cytoplasmic for E-cadherin and cytoplasmic and/or nuclear for β-catenin) was observed, whereas only a minority of cases revealed normal membranous distribution of the labeling. The present study is the first in the literature to reveal a correlation between the expression of E-cadherin and β-catenin and the examined Cxs in CRC in humans. The positive correlation between the Cxs, particularly Cx26 and Cx32, and the adhesive proteins occurred in patients without lymph node metastases and in the moderately differentiated tumors (G2). Such a dependency was not observed in the analysis of the correlation between Cx43 and E-cadherin. However, a positive correlation between these proteins was observed in patients with lymph nodes metastases. Additionally, a link between the expression of these adhesion proteins was observed. The present study indicates, for the first time, that the expression of adhesion proteins, E-cadherin and β-catenin, is closely associated with the expression of three studied Cxs in CRC, and that this correlation may improve an understanding of the carcinogenic process in this cancer.

Connexins, E-cadherin, Claudin-7 and β-catenin transiently form junctional nexuses during the post-natal mammary gland development

“…Using an immunoprecipitation assay, we first demonstrated that Cx32 interacts with E-cadherin and β-catenin at both tested time point. Although Cx32 co-localization and co-regulation with E-cadherin and β-catenin have been observed in other tissues (Schwarz, Wanke et al 2003) (Kanczuga-Koda, Wincewicz et al 2014) (Ionta, Rosa et al 2012) (Plante, Cyr et al 2005) (Plante, Charbonneau et al 2006), to our knowledge, this is the first report of their physical interaction.…”

“…Cxs interact and coimmunoprecipitate with a variety of structural and signaling molecules, such as tubulin (Giepmans, Verlaan et al 2001), zonula occluden-1 (ZO-1), catenins (Ai, Fischer et al 2000) (Xu, Li et al 2001), occludin, N-cadherin (Wei, Francis et al 2005) and Src proteins (Duffy, Delmar et al 2002); additionally, they co-localize with adherens and tight junctions (AJs and TJs, respectively) (Angst, Khan et al 1997). Thus, GJs, AJs and TJs may form a junctional nexus in which the different components are regulated by common pathways and might then regulate each other's functions and localization (Ai, Fischer et al 2000) (Giepmans 2004) (Hertig, Eppenberger-Eberhardt et al 1996) (Jongen, Fitzgerald et al 1991) (Kurley, Bierie et al 2012) (Xu, Li et al 2001) (Ale-Agha, Galban et al 2009) (Kanczuga-Koda, Wincewicz et al 2014) (Jongen, Fitzgerald et al 1991) (Fujimoto, Nagafuchi et al 1997).…”

The Role of E-Cadherin in Maintaining the Barrier Function of Corneal Epithelium after Treatment with Cultured Autologous Oral Mucosa Epithelial Cell Sheet Grafts for Limbal Stem Deficiency

“…It is well known that the E-cadherin/beta-catenin complex regulates gap junction proteins, such as Cnx43, because E-cadherin/beta-catenin complex loss was found associated with Cnx43 loss at the cell membranes [ 42 , 43 ]. Cnx43 levels and expression in CAOMECS grafts were similar to normal corneal epithelium.…”

Connexin and pannexin channels in cancer

“…Cx43 was also found to protect glioblastoma cells against radiation-induced DNA damage. The correlation of expression of adhesion molecules and connexin subtypes is also investigated in human colorectal cancer; a positive correlation between Cx26 and Cx32, but not Cx43 and adhesive proteins in patients without lymph node metastases while a positive association between Cx43 and E-cadherin with lymph node metastases [ 129 ]. Cx43 expression is correlated with oral squamous cell carcinoma and the overall survival time, and is proposed as an independent prognostic biomarker [ 130 ].…”