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Query: UNIPROT:B0FTZ7 (catenin)
 18,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The E-cadherin/catenin complex is a calcium-dependent cell-cell adhesion molecule, whose function is critical to the integrity of the adherens junction and which plays a role in the establishment and maintenance of normal epithelial morphology and differentiation. Loss of E-cadherin-mediated adhesion appears to be a fundamental aspect of the neoplastic phenotype which in some cases appears to be mediated by post-translational modifications (i.e. tyrosine phosphorylation) of its interacting proteins, the catenins which link E-cadherin to the actin cytoskeleton. There is increasing experimental evidence to suggest that epidermal growth factor receptor tyrosine phosphorylation may lead to the inactivation of the E-cadherin/catenin complex in cancer cells through its interaction with beta- or gamma-catenin in the cytoskeleton. Modulation of epidermal growth factor receptor activity by pharmacological agents has the potential to regulate a variety of cellular processes including adhesion, differentiation, and proliferation.
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PMID:The E-cadherin/epidermal growth factor receptor interaction: a hypothesis of reciprocal and reversible control of intercellular adhesion and cell proliferation. 1036 89

beta-catenin plays a fundamental role in the regulation of the E-cadherin-catenin cell adhesion complex. It also functions in growth signalling events, independently of the cadherin-catenin complex, and these signalling pathways are disturbed in colorectal cancer. Mutations in either the APC or beta-catenin genes in colorectal cancer cells result in up-regulation of protein expression and subsequent cytoplasmic and nuclear distribution of beta-catenin. In this study, we examined beta-catenin expression in 47 primary colorectal tumors and the corresponding liver metastases. Immunohistochemical studies demonstrated loss of membranous beta-catenin expression in 26% of primary tumors and 60% of liver metastases and a concomitant increase in cytoplasmic and nuclear staining. Widespread nuclear expression of beta-catenin was found in 64% of primary tumors and 21% of liver metastases. No associations were found between any form of beta-catenin expression and either tumor stage or tumor grade. Cellular distribution of beta-catenin was also examined by detergent extraction and Western blot analysis in 16 primary tumors and 23 liver metastases. This analysis showed that most tumors demonstrated reduced beta-catenin in the cytoskeletal fraction and increased beta-catenin in the cytosolic fraction. Furthermore, 3 liver metastases were found to contain a truncated beta-catenin protein of approximately M(r) 80,000. Immunoprecipitation studies showed that the truncated beta-catenin proteins only bound weakly to E-cadherin and beta-catenin compared with non-truncated beta-catenin. These results demonstrate gross alterations in the cellular distribution of beta-catenin in primary colorectal cancers with metastatic potential, as well as in the metastatic tumors. These changes may be the consequence of APC or beta-catenin gene mutations, or possibly result from a post-translational modification of the E-cadherin-catenin complex.
Int J Cancer 1999 Aug 12
PMID:beta-catenin expression in primary and metastatic colorectal carcinoma. 1040 62

Dysfunction of the cadherin-catenin complex, a key component of adherens junctions, is thought to confer invasive potential to cells. The aim of this study is to examine the expression and function of the E-cadherin/catenin complex in gastric carcinoma cell lines. Expression of E-cadherin, alpha, beta and gamma-catenin and p120ctn, and of the adenomatous polyposis coli protein (APC), together with function of the cadherin-catenin complex was examined in a panel of gastric carcinoma cell lines, using immunocytochemistry, Western blotting and a cell-cell aggregation assay. Protein interactions were examined by sequential immunoprecipitation and immunoblotting with antibodies to E-cadherin, alpha, beta and gamma-catenin, p120ctn and APC. Abnormalities of E-cadherin, alpha- and beta-catenin expression, were associated with disturbance of E-cadherin-catenin complex composition, loss of membranous localization and loss of calcium-dependent aggregation in six gastric carcinoma cell lines. APC protein expression and interaction with beta-catenin was preserved in five cell lines. We demonstrate frequent abnormalities of expression and function of E-cadherin and catenins, and associated disturbance of E-cadherin-mediated intercellular adhesion in gastric carcinoma cell lines. These findings support the tumour suppressor role of the E-cadherin and its contribution to the development and progression of the neoplastic phenotype in gastric carcinoma.
Br J Cancer 1999 May
PMID:Abnormal expression and function of the E-cadherin-catenin complex in gastric carcinoma cell lines. 1040 33

Normally functioning cell-cell adhesion plays an important role in the maintenance of tissue architecture and cell cohesion. E-cadherin is an important adhesion molecule of epithelial cells. In many types of cancer the expression of E-cadherin is reduced leading to increased risk of disease progression. alpha-Catenin is one of the intracellular elements of the E-cadherin-catenin complex. The abnormalities in the expression of alpha-catenin seem to associate with malignant cellular features and disease progression in prostate cancer. To further analyse the significance of alpha-catenin expression, we studied 215 cases of prostate cancer by immunohistochemistry and the results were related to other known prognostic factors and patient survival during a mean follow-up period of 13 years. alpha-Catenin expression was down-regulated in 19% of the cases and 3% of the tumours were totally alpha-catenin-negative. The abnormal alpha-catenin expression and cytoplasmic signal were significantly linked with high T-category, metastatic disease, high Gleason score, perineural growth, high mitotic rate, high S phase fraction and DNA aneuploidy (P < 0.05 for all). In the survival analysis, reduced alpha-catenin expression (P = 0.06) and cytoplasmic signal (P = 0.04) were related to unfavourable patient outcome. In the multivariate analysis, including TM-classification and Gleason score, alpha-catenin expression had independent prognostic value in T1-2 M0 tumors. In the M0 tumours, abnormal alpha-catenin signal was independently associated with recurrence-free survival as well. The results indicate that down-regulation of alpha-catenin is related to several malignant cellular features, and it seems to have prognostic significance in the early phases of cancer progression. We suggest that alpha-catenin expression can provide prognostic information in early prostate cancer.
Br J Cancer 1999 May
PMID:Alpha-catenin expression has prognostic value in local and locally advanced prostate cancer. 1040 56

Cell-cell contacts are important regulatory elements in tissue development, organ morphogenesis and malignant tumor invasion. In recent in vivo studies we have identified the members of the cadherin/catenin family of cell adhesion proteins that are differentially expressed in the pancreas and have determined their cell biological dynamics during dissociation and repair of adherens junctions. To further characterize these events, epithelial cell culture systems were used and a number of type II protein tyrosine phosphatases (PTPs) were found to colocalize and interact with the cadherin/catenin complex. These observations suggest that tyrosine dephosphorylation in general and PTPs in particular are involved in cell contact formation. Our most recent experiments indicate 1) that inhibition of PTPs alone dissociates pancreatic adherens junctions, 2) that cytosolic and transmembrane PTPs are differentially expressed in acinar cells, and 3) that a subset of them can associate with proteins of the cadherin/catenin complex at pancreatic cell-cell adhesions.
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PMID:Protein tyrosine dephosphorylation and the maintenance of cell adhesions in the pancreas. 1041 59

The E-cadherin/catenin complex plays an essential role in maintaining intimate intercellular associations and is considered to be involved in tumor metastasis and suppressing invasion by cancer cells. We have analyzed the expression of E-cadherin/catenin complex in a series of nasopharyngeal carcinoma (NPC) specimens using immunohistochemistry and immunoblotting. Data are correlated with the patients' clinicopathological parameters, including the clinical stage, presence of intracranial invasion, presence of lymph node or distant metastasis, and histological grading. The E-cadherin/catenin complex is down-expressed in most of the samples examined. Correlation with clinicopathological parameters shows that expression of alpha- and beta-catenin is associated with the occurrence of intracranial invasion.
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PMID:Expression of E-cadherin/catenin complex in nasopharyngeal carcinoma: correlation with clinicopathological parameters. 1042 4

Mutations in the adenomatous polyposis coli gene or activating mutations in the beta-catenin gene itself are thought to be responsible for the excessive beta-catenin signaling involved in intestinal carcinogenesis. We generated transgenic mice that expressed large amounts of a NH2-terminally truncated mutant beta-catenin (deltaN131beta-catenin) in the intestine. These mice had multifocal dysplastic lesions in the small intestine, reminiscent of the early lesions observed in the mouse models of familial adenomatous polyposis. The number of apoptotic cells in the villi of these transgenic mice was 3-4-fold higher than in nontransgenic mice. Expression of the truncated beta-catenin mutant in the kidney led to the development of severe polycystic kidney disease. Our findings support the concept that deregulation of the beta-catenin signaling pathway is the major oncogenic consequence of adenomatous polyposis coli mutations in intestinal neoplasia.
Cancer Res 1999 Aug 15
PMID:Intestinal dysplasia and adenoma in transgenic mice after overexpression of an activated beta-catenin. 1046 73

Cadherins are transmembrane cell-cell adhesion molecules which are connected to the cytoskeleton by association with the cytoplasmic proteins, alpha-, beta-, and, gamma-catenin (plakoglobin). Beta-catenin has an additional role in the wnt signal transduction pathway in which it transmitts signals to the cell nucleus in complexes with transcription factors of the LEF-1/TCF family. The cell adhesion function of the epithelial E-cadherin is frequently disturbed in carcinomas either by downregulation or by mutation of the E-cadherin/catenin genes. The signaling function of beta-catenin is activated in tumors by mutations of beta-catenin or of the tumor suppressor gene product APC. In this review I will give an introduction to the structure and function of the cadherin/catenin complex and summarize findings which support a decisive role of these components in the development of cancer.
Cancer Metastasis Rev 1999
PMID:Cadherins and catenins: role in signal transduction and tumor progression. 1050 43

The E-cadherin/catenin protein complex regulates the functional integrity of epithelia by mediating specific intercellular adhesion, Defects in the transmembrane E-cadherin protein play an important role in several human cancer types. E-cadherin-inactivating mutations were mainly found in sporadic lobular breast carcinoma and in both familial and sporadic diffuse gastric carcinoma. Armadillo proteins such as beta-catenin and p120ctn are complexed to the cytoplasmic tail of E-cadherin, whereas the vinculin-related alphaE-catenin protein forms a link to the actin cytoskeleton. The latter shows inactivating deletions in various tumor cell lines. Apparently, both E-cadherin and alphaE-catenin serve as tumor suppressor and invasion suppressor molecules. On the other hand, protein-stabilizing oncogenic mutations of beta-catenin were found at high frequency in particular human tumor types. Mutated beta-catenin protein is imported into the nucleus, and its binding to LEF/TCF transcription factors modulates transcription of intriguing target genes. Also p120ctn was recently found to arrive in the nucleus and to interact with a transcription factor. Furthermore, a wide variety of mechanisms have been described to regulate in a reversible way E-cadherin/catenin-mediated cell adhesion and differentiation. These phenomena appear to be crucial in human cancer development and progression.
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PMID:The role of the E-cadherin/catenin adhesion complex in the development and progression of cancer. 1054 29

The cadherin/catenin complex plays a key role in the initiation of cell-cell recognition, and adhesion, and the elaboration of structural and functional organization in multicellular tissues and organs. It is associated with tumor metastasis and also acts as an "invasion suppressor" of cancer cells. Nasopharyngeal carcinoma (NPC) is notorious for its highly metastatic nature. The expression of the E-cadherin/catenin complex is down-regulated in NPC tumor specimens. To obtain better insight into the intercellular adhesive property of NPC cells, we used immunofluorescence microscopy, immunoprecipitation, and immunoblot analysis to examine the expression of the classical cadherins and beta-catenin in a NPC cell line, TW-039. The results demonstrate a change in the distribution of E-cadherin from cytosolic flakes to cell-cell contacts with increasing time in culture. Between days 1 and 5 after plating, the detergent-insoluble fraction of E-cadherin increased from 20% to 37% of total E-cadherin, and that for P-cadherin increased from 33% to 40%. By contrast, the values for beta-catenin remained unchanged (26% and 25%). Both immunofluorescence and immunoblot studies suggested that P-cadherin may be involved in pioneer contact adhesion of TW-039 cells. Interestingly, E-, P-, and N-cadherin are co-expressed in this cell line. Immunoprecipitation studies also showed that other members of the cadherin family may be involved in the contact adhesion of TW-039 cells.
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PMID:E-, P-, and N-cadherin are co-expressed in the nasopharyngeal carcinoma cell line TW-039. 1058 Oct 10


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