Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:B0FTZ7 (catenin)
 18,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Morphology at both cellular and glandular levels in the colon is dependent to an extent on cell-cell adhesion mediated by cadherin-catenin complexes. Alterations in the expression of E-cadherin, the cadherin normally present in colon, have been shown to be implicated in tissue remodelling within the gastrointestinal tract. Furthermore, it has previously been shown that P-cadherin, normally present only in stratified epithelia and placenta, is expressed in colitis and during neoplastic change in the colon. The morphological features of mucosal injury induced by pre-operative radiotherapy in the non-neoplastic rectal mucosa were studied in patients with rectal adenocarcinoma. Three characteristic phases of radiation proctitis were defined on histological grounds (acute injury, and early and late regenerative phases) essentially correlating with the time interval between radiotherapy and surgery; such features were mirrored by alterations in cadherin-catenin expression and localization in rectal crypts. On immunohistochemistry and western blotting, P-cadherin was highly expressed in the acute injury and early regenerative phases, with a decreased level of expression during late regeneration. E-cadherin and associated catenins were translocated from membrane to cytoplasm in degenerating crypts, with return of normal membranous expression in regenerating crypts. In conclusion, radiation-induced proctitis represents an in vivo model of mucosal injury and regeneration and provides a valid model in which to study events during epithelial injury and repair. Altered cadherin expression, in particular transient aberrant P-cadherin expression, is intimately associated with these processes.
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PMID:Transient P-cadherin expression in radiation proctitis; a model of mucosal injury and repair. 1201 43

The cadherin/catenins complex regulates cell-cell adhesion and motility and is believed to have an invasion suppressor role. Primary mucoepidermoid carcinoma of the thyroid (MECT) is a rare tumour characterised by a distinct morphological appearance and a questionable histogenesis. The coexistence of papillary thyroid carcinoma (PTC) foci in many patients with MECT suggests an association between the two tumour histotypes. In an attempt to clarify the putative relationship between MECT and PTC, we analysed tissue from 11 patients with MECT by immunohistochemistry (E-, P- and N-cadherins and alpha-, beta- and gamma-catenins). The E-cadherin gene was also analysed by polymerase chain reaction (PCR)/single-strand conformation polymorphism (SSCP). The results were compared with a control group of normal thyroid, classical PTC and the diffuse sclerosing variant of PTC. Compared with normal thyroid and PTC, MECT displays marked abnormalities of the cadherin/catenin complex. Such abnormalities include the consistent neoexpression of P-cadherin and major alterations in the expression of E-cadherin and the three catenins. Our results point to the close relationship between the de novo expression of P-cadherin and the disruption of the cadherin/catenins complex with the squamoid phenotype of MECT.
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PMID:Mucoepidermoid carcinoma of the thyroid: a tumour histotype characterised by P-cadherin neoexpression and marked abnormalities of E-cadherin/catenins complex. 1202 24

The cadherin-catenin complex regulates cellular adhesion and motility, and genetic alterations in these molecules play a critical role in multistage tumorigenesis. In this study, the expression of three major type I classic cadherins E-, N-, and P-cadherin and their undercoat proteins alpha-, beta-, and gamma-catenin, and pp120 was investigated in 127 pituitary adenomas and 10 normal adenohypophyseal glands using an immunohistochemical technique with highly specific monoclonal antibodies. In normal pituitary glands, E-cadherin, catenins, and pp120 were strongly expressed on almost all hormone-producing cell-cell boundaries, N-cadherin was weakly immunoreactive on a few cell-cell boundaries, and P-cadherin was negative. In pituitary adenomas, a correlation was not identified among expression of E-cadherin, catenins, or pp120 with patient age, sex, hormone level, tumor size, and/or invasiveness, respectively. Expression of E-cadherin, catenins, and pp120 was significantly reduced in 24 growth hormone (GH) cell adenomas with prominent fibrous bodies compared with the other subtypes of pituitary adenomas and normal pituitary glands (p < 0.0001, respectively). Methylation-specific polymerase chain reaction analysis revealed that the E-cadherin gene promoter region was methylated in 6 of 16 (37.5%) GH cell adenomas with prominent fibrous bodies examined, 2 of which displayed total methylation, but not in 10 GH cell adenomas without fibrous bodies. No mutation of exon 3 of the beta-catenin gene was found in 16 GH cell adenomas with prominent fibrous bodies or in 10 other subtypes of pituitary adenomas that showed unremarkable intracellular presence of beta-catenin protein. In conclusion, the decreased expression of the E-cadherin catenin complex and methylation of the E-cadherin gene promoter region only in GH cell adenomas with prominent fibrous bodies may be an event associated with the formation of fibrous bodies.
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PMID:Downregulation of E-cadherin and its undercoat proteins in pituitary growth hormone cell adenomas with prominent fibrous bodies. 1266 52

Smad4 is a tumour suppressor gene predominantly involved in gastrointestinal carcinogenesis. Loss of Smad4 is considered to be a genetically late step and occurs in up to 30% of metastatic colorectal carcinomas. Smad4, originally characterized as an intracellular transmitter of transforming growth factor-beta (TGF-beta) signals, is a transcriptional co-modulator capable of integrating cellular responses to multiple signalling cascades. Thus, there are many Smad4 target genes and they are presumably strongly context-dependent. It was recently shown that re-expression of Smad4 in Smad4-deficient SW480 human colon carcinoma cells restored epithelioid morphology and induced P-cadherin and E-cadherin transcription. The cadherins are key players in cell-cell adhesion connecting adjacent cells via the cadherin-catenin adhesion complex. Frequent loss of E-cadherin expression in human cancers has been a long-standing observation, but the underlying mechanisms are not yet fully understood. To assess the role of Smad4 in E-cadherin regulation in colorectal carcinogenesis further, the present study has analysed Smad4 and E-cadherin RNA and protein expression in colorectal carcinoma cell lines and in 51 late-stage colorectal carcinomas. In primary tumours, loss of Smad4 expression correlated highly significantly with loss of E-cadherin expression, thus providing further evidence for involvement of the tumour suppressor Smad4 in the control of expression of the tumour and invasion suppressor E-cadherin.
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PMID:Loss of Smad4 correlates with loss of the invasion suppressor E-cadherin in advanced colorectal carcinomas. 1509 68

E-cadherin functions as suppressor of invasion in epithelial cells and its loss is described in many invasive carcinomas. In some tumours, the disappearance of E-cadherin has been correlated with upregulation of other classical cadherins, such as N- or P-cadherin. To analyse the different cellular functions of cadherin molecules, we stably expressed E-cadherin or N-cadherin in the E- and N-cadherin-deficient pancreatic tumour cell line MIA PaCa-2. Only E-cadherin was able to induce a mesenchymal-epithelial transition and suppressed invasion of MIA PaCa-2 cells. Furthermore, only re-expression of E-cadherin resulted in an upregulation of alpha- and beta-catenin mRNAs and protein concentrations. Ectopically expressed N-cadherin failed to assemble cadherin/catenin adhesion complexes and failed to inhibit invasion. Analysis of p120(ctn), which was associated with both cadherins, demonstrated that E-cadherin was linked to a shorter isoform of p120(ctn). In contrast, N-cadherin was associated with the long, 120 kDa p120(ctn) isoforms. In addition, p120(ctn) connected with N-cadherin was phosphorylated at tyrosine residues, whereas the isoform linked to E-cadherin was not phosphorylated. Thus, the differences between E- and N-cadherin in recruiting different phosphorylated isoforms of p120(ctn) to the membrane might be responsible for the inability of N-cadherin to replace E-cadherin as suppressor of invasion in pancreatic carcinoma cells.
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PMID:E- and N-cadherin differ with respect to their associated p120ctn isoforms and their ability to suppress invasive growth in pancreatic cancer cells. 1510 17

Cadherins and their associated cytoplasmic proteins, catenins, are critical to the maintenance of normal tissue integrity and the suppression of cancer invasion. The cadherin profile in malignant mesothelioma (MM) is not well defined and the role of the cadherin-catenin system in the pathogenesis of MM remains to be determined. By means of Western blot analysis and immunohistochemistry the expression of E (epithelial)-, N (neural)-, P (placental)-cadherin, and alpha-, beta- and gamma-catenins was studied in nine human MM cell lines and five human mesothelial cell lines. Mesothelial cells consistently expressed only N-cadherin and alpha- and beta-catenins. All but one MM cell line were N-cadherin-positive and all of them were also positive for alpha- and beta-catenins. E-cadherin was found in six (66.7%) and gamma-catenin in seven (77.8%) MM cell lines. Five of these E-cadherin-positive lines co-expressed N-cadherin and the remaining one was also P-cadherin-positive. Double immunofluorescence staining revealed the plasma membrane co-localisation of both cadherin types in MM cell lines that co-expressed E- and N-cadherin or E- and P-cadherin, respectively. Immunoprecipitation showed complexes of beta-catenin with both cadherin types when co-expressed. The results point to upregulation of E-cadherin and gamma-catenin in most MM cases and demonstrate that cadherin expression is more heterogeneous and less mutually exclusive in MM compared with the mesothelium, although the biological significance of this finding remains unclear.
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PMID:Aberrant E-cadherin and gamma-catenin expression in malignant mesothelioma and its diagnostic and biological relevance. 1526 32

Alterations in the cadherin-catenin expression and activation of the Wnt signaling have been related to the pathology of ovarian carcinomas. Here, we evaluated the immunoreactivity of cadherins (E-, P-, and N-cadherin and cadherin-11) and catenins (alpha-, beta-, and gamma-catenin and p120) in 86 ovarian tumors. We found significant differences in the expression of all cadherins and catenins among the distinct histologic tumor types. Clear cell tumors were rarely N-cadherin- and P-cadherin-positive and showed reduced membranous expression in all the catenins; Serous carcinomas were frequently N-cadherin- and P-cadherin-positive, mucinous tumors strongly expressed E-cadherin and the catenins in the membrane, and endometrioid tumors characteristically expressed nucleocytoplasmic beta-catenin in most of the cases. We next studied whether allelic losses in the chromosomal regions containing various cadherin genes (16q22) or APC gene (5q21) occurred in ovarian tumors and observed a high frequency of loss of heterozygosity in 16q22 (78%) and 5q21 (33%) regions, but there were no differences among the tumor types analyzed. Finally, we also assessed the molecular alterations responsible for beta-catenin nuclear accumulation in endometrioid tumors by screening for mutations in AXIN1, AXIN2, APC, and KRAS genes. Mutations in KRAS were observed in 2 of 19 tumors, but no mutations were detected in AXIN1, AXIN2, or APC genes. Only beta-catenin gene mutations were associated with nuclear beta-catenin staining in these tumors. In conclusion, different cadherin-catenin expression patterns are associated with distinct histologic types. Oncogenic Wnt signaling plays a role only in endometrioid tumors, where beta-catenin mutations seem to be the main cause of its aberrant expression.
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PMID:Expression of cadherins and catenins correlates with distinct histologic types of ovarian carcinomas. 1686 67

In the present review article the role of cadherin/catenin complex in cases of malignant melanoma is discussed in some detail. Cadherins represent the most important superfamily of adhesion molecules with epithelial E-cadherin being the most studied. Its role in normal state as well as in cancer invasion and metastasis and some other pathologies is crucial. E-cadherin expression is altered in malignant melanomas and its downregulation or absence is associated with melanoma invasion and metastasis potential. A shift from E-cadherin expression to neural N-cadherin expression in melanocytes is also detected in malignant melanomas formation. In addition, a discussion regarding the role of placental P-cadherin and vascular endothelial VE-cadherin as well as the recently identified molecule of dysadherin, is attempted in brief.
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PMID:The role of cadherin/catenin complex in malignant melanoma. 1708 10

Densin is a member of LAP (leucine-rich repeat and PDZ domain) protein family that localizes in kidney to slit diaphragms, which are essential components of the glomerular filtration barrier. We have previously shown that densin interacts with a crucial slit diaphragm protein, nephrin. Here, we searched for novel binding partners of densin by yeast-two hybrid assay and identified beta-catenin. The interaction was confirmed by reciprocal co-immunoprecipitation assay and the binding site in densin was determined by GST-pull down assays. The GST-tagged densin was also able to pull down P-cadherin together with beta-catenin from human kidney glomerular lysates. Furthermore, densin co-localized with beta-catenin and F-actin in cell-cell contacts in cultured mouse podocytes. During cell-cell contact disruption and reformation densin and beta-catenin were dislocated from and relocated back to plasma membrane in a similar fashion. These and our previous findings suggest that densin may associate with the cadherin-catenin and nephrin complex(es), and may be involved in the formation of the cell-cell contacts including the slit diaphragm.
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PMID:Densin and beta-catenin form a complex and co-localize in cultured podocyte cell junctions. 1758 99

Cadherin-catenin complexes play a critical role in intercellular adhesion, and their altered expression has been implicated in tumour progression. In this study, the expression of E-cadherin, P-cadherin and beta-catenin was analysed in 65 canine malignant mammary tumours and correlated with clinicopathological parameters, proliferation and survival. Reduction in E-cadherin expression was significantly associated with increased tumour size, high histological and invasion grades, lymph node metastasis and high mitotic index. Reduced beta-catenin expression was associated with high histological and invasion grades. Anomalous expression of P-cadherin was only associated with invasion. In 39 cases for which follow-up data were available, reduced E-cadherin and beta-catenin expression was significantly associated with shorter overall survival and disease free survival. Abnormal expression of adhesion molecules is a common phenomenon in canine mammary malignant tumours and may play a central role in tumour progression.
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PMID:Expression of E-cadherin, P-cadherin and beta-catenin in canine malignant mammary tumours in relation to clinicopathological parameters, proliferation and survival. 1805 5


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