| http://purl.uniprot.org/citations/30285466 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/30285466 | http://www.w3.org/2000/01/rdf-schema#comment | "Adherens junctions (AJs), together with tight junctions (TJs), form an apical junctional complex that regulates intestinal epithelial cell-to-cell adherence and barrier homeostasis. Within the AJ, membrane-bound E-cadherin binds β-catenin, which functions as an essential intracellular signaling molecule. We have previously identified a novel protein in the region of the apical junction complex, chloride channel protein-2 (ClC-2), that we have used to study TJ regulation. In this study, we investigated the possible effects of ClC-2 on the regulation of AJs in intestinal mucosal epithelial homeostasis and tumorigenicity. Mucosal homeostasis and junctional proteins were examined in wild-type (WT) and ClC-2 knockout (KO) mice as well as associated colonoids. Tumorigenicity and AJ-associated signaling were evaluated in a murine colitis-associated tumor model and in a colorectal cancer cell line (HT-29). Colonic tissues from ClC-2 KO mice had altered ultrastructural morphology of intercellular junctions with reduced colonocyte differentiation, whereas jejunal tissues had minimal changes. Colonic crypts from ClC-2 KO mice had significantly higher numbers of less-differentiated forms of colonoids compared with WT. Furthermore, the absence of ClC-2 resulted in redistribution of AJ proteins and increased β-catenin activity. Downregulation of ClC-2 in colorectal cells resulted in significant increases in proliferation associated with disruption of AJs. Colitis-associated tumors in ClC-2 KO mice were significantly increased, associated with β-catenin transcription factor activation. The absence of ClC-2 results in less differentiated colonic crypts and increased tumorigenicity associated with colitis via dysregulation of AJ proteins and activation of β-catenin-associated signaling. NEW & NOTEWORTHY Disruption of adherens junctions in the absence of chloride channel protein-2 revealed critical functions of these junctional structures, including maintenance of colonic homeostasis and differentiation as well as driving tumorigenicity by regulating β-catenin signaling."xsd:string |
| http://purl.uniprot.org/citations/30285466 | http://purl.org/dc/terms/identifier | "doi:10.1152/ajpgi.00087.2018"xsd:string |
| http://purl.uniprot.org/citations/30285466 | http://purl.uniprot.org/core/author | "Jin Y."xsd:string |
| http://purl.uniprot.org/citations/30285466 | http://purl.uniprot.org/core/author | "Magness S.T."xsd:string |
| http://purl.uniprot.org/citations/30285466 | http://purl.uniprot.org/core/author | "Ibrahim D."xsd:string |
| http://purl.uniprot.org/citations/30285466 | http://purl.uniprot.org/core/author | "Blikslager A.T."xsd:string |
| http://purl.uniprot.org/citations/30285466 | http://purl.uniprot.org/core/date | "2018"xsd:gYear |
| http://purl.uniprot.org/citations/30285466 | http://purl.uniprot.org/core/name | "Am J Physiol Gastrointest Liver Physiol"xsd:string |
| http://purl.uniprot.org/citations/30285466 | http://purl.uniprot.org/core/pages | "G966-G979"xsd:string |
| http://purl.uniprot.org/citations/30285466 | http://purl.uniprot.org/core/title | "Knockout of ClC-2 reveals critical functions of adherens junctions in colonic homeostasis and tumorigenicity."xsd:string |
| http://purl.uniprot.org/citations/30285466 | http://purl.uniprot.org/core/volume | "315"xsd:string |
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