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)

During early heart development the expression pattern of N-cadherin, a calcium-dependent cell adhesion molecule, suggests its involvement in morphoregulation and the stabilization of cardiomyocyte differentiation. N-cadherin's adhesive activity is dependent upon its interaction with the intracellular catenins. An association with alpha-catenin and beta-catenin also is believed to be involved in cell signaling. This study details the expression patterns of alpha-catenin, beta-catenin, and gamma-catenin, during definition of the cardiac cell population as distinct compartments in the anterior regions of the chick embryo between stages 5 and 9. The restriction of N-cadherin/catenin localization at stage 5+ from a uniform pattern in vivo, to specific cell clusters that demarcate areas where mesoderm separation is initiated, suggests that the N-cadherin/catenin complex is involved in boundary formation and in the subsequent cell sorting. The latter two processes lead to the specification and formation of the somatic and cardiac splanchnic mesoderm. N-cadherin colocalized with alpha- and beta-catenin at the cell membrane before and during the time that its expression becomes restricted to the lateral mesoderm and continues cephalocaudad into stage 8. These proteins continue to colocalize in the myocardium of the tubular heart. Plakoglobin is not expressed in this region during stages 6-8, but is detected in the myocardium later at stage 13. The observed in vivo expression patterns of alpha-catenin, beta-catenin, and plakoglobin suggest that these proteins are directly linked with the developmental regulation of cell junctions, as cardiac cells become stably committed and phenotypically differentiated to eventually form a mature myocardium. The localization of N-CAM also was analyzed during these stages to determine whether the N-cadherin-catenin localization was unique or whether other cell adhesion molecules were expressed similarly. The results indicate that the unique pattern of N-cadherin expression is not shared with N-CAM. We also show that perturbation of N-cadherin using a function perturbing N-cadherin antibody (NCD-2) inhibits normal early heart development and myogenesis in a cephalocaudad, stage-dependent manner. We propose a model whereby myocardial cell compartmentalization also defines the endocardial population. The presence of beta-catenin suggests that a similar signaling pathway involving Wnt (wingless)-mediated events may function in myocardial cell compartmentalization during early vertebrate heart development, as in Drosophila contractile vessel development.
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PMID:N-cadherin-catenin interaction: necessary component of cardiac cell compartmentalization during early vertebrate heart development. 918 80

E-cadherin is crucial to the intercellular adherens junctions which are involved in the organisation and maintenance of epithelial structure and suppression of tumour invasion. E-cadherin is associated with the actin cytoskeleton via cytoplasmic proteins, including alpha-, beta- and gamma-catenins, which together form the cadherin/catenin complex. To evaluate changes of the molecules of the cadherin/catenin complex in colorectal carcinogenesis, seventy-four sporadic adenomas, samples of histologically normal epithelium adjacent to 65 adenomas, and 52 carcinomas arising in adenomas were investigated by immunohistochemistry. All normal epithelial cells showed a uniform membranous staining pattern for E-cadherin, alpha-, beta-, and gamma-catenin. Decreased expression of all 4 proteins occurred in parallel in adenomas and carcinomas (in all cases, p < 10(-5). Decreased expression of the cadherin/catenin complex in adenomas was associated with increasing severity of dysplasia (p < 0.001, for E-cadherin, alpha-, and gamma-catenin, p < 0.005 for beta-catenin). Carcinomas displayed significantly reduced expression of the cadherin/catenin complex compared with their associated adenomas (all p < 0.001). The results directly confirm that colorectal tumour progression and invasion is associated with disruption of the cadherin/catenin complex and suggest that the genetic changes and transcriptional modulation of catenins underlying this progression may affect all members of the complex.
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PMID:Reduced expression of molecules of the cadherin/catenin complex in the transition from colorectal adenoma to carcinoma. 921 95

During the progression of many cancers, cell-cell adhesion molecules, e.g., E-cadherin (EC), may be down-regulated. In a number of carcinomas, EC has been described as an independent prognostic variable. We have studied the expression of adhesion molecules participating in cadherin-catenin complexes in renal cell carcinoma (RCC) specimens. Expression of EC, catenins and p120cas protein was examined in frozen tissue of 90 RCC specimens by immunohistochemistry, and these molecules were evaluated for their significance as prognostic markers. Staining was scored as normal (homogeneously positive at cell-cell borders) or abnormal (heterogeneous or absent). A significant correlation between poor survival and decreased expression of alpha-, beta- or gamma-catenin was observed, whereas no association between survival and EC or p120cas expression was seen. Cox's proportional hazard regression analysis showed that in patients with pT1-3N0M0 disease, reduced alpha-catenin expression correlated with poor survival, suggesting that alpha-catenin expression might be an independent prognostic indicator for patients of this group.
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PMID:Decreased expression of alpha-catenin is associated with poor prognosis of patients with localized renal cell carcinoma. 935 75

The integrity of the vascular endothelium is mainly dependent upon the organization of interendothelial adherens junctions (AJ). These junctions are formed by the homotypic interaction of a transmembrane protein, vascular endothelial cadherin (VE-cadherin), which is complexed to an intracellular protein network including alpha-, beta-, and gamma-catenin. Additional proteins such as vinculin and alpha-actinin have been suggested to link the VE-cadherin/catenin complex to the actin-based cytoskeleton. During the process of hematogenous metastasis, circulating tumor cells must disrupt these intercellular junctions in order to extravasate. In the present study, we have investigated the influence of tumor cell-endothelial cell interaction upon interendothelial AJ. We show that human breast adenocarcinoma cells (MCF-7), but not normal human mammary epithelial cells, induce a rapid endothelial cell (EC) dissociation which correlates with the loss of VE-cadherin expression at the site of tumor cell-EC contact and with profound changes in vinculin distribution and organization. This process could not be inhibited by metalloproteinase nor serine protease inhibitors. Immunoprecipitations and Western blot analysis demonstrate that the overall expression of VE-cadherin and vinculin as well as the composition of the VE-cadherin/catenins complex are not affected by tumor cells while the tyrosine phosphorylation status of proteins within the complex is significantly altered. Our data suggest that tumor cells modulate AJ protein distribution and phosphorylation in EC and may, thereby, facilitate EC dissociation.
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PMID:Alteration of interendothelial adherens junctions following tumor cell-endothelial cell interaction in vitro. 943 30

Loss of expression of the intercellular adhesion molecule E-cadherin frequently occurs in invasive lobular breast carcinomas as a result of mutational inactivation. Expression patterns of E-cadherin and the molecules comprising the cytoplasmic complex of adherens junctions, alpha-, beta- and gamma-catenin, were studied in a series of 38 lobular breast carcinomas with known E-cadherin mutation status. The effect of loss of E-cadherin by mutational inactivation (or other mechanisms) on the expression of catenins was investigated. Complete loss of plasma membrane-associated E-cadherin expression was observed in 32 out of 38 invasive lobular carcinomas, for which in 21 cases a mutation was found in the extracellular domain of E-cadherin. In total, 15 frameshift mutations of small deletions or insertions, ranging from 1 to 41 bp, three non-sense mutations, and three splice mutations were identified. Mutations were scattered over the whole coding region and no hot spots could be detected. In all cases, simultaneous loss of E-cadherin and alpha- and beta-catenin expression was found; in 50 per cent of these cases, additional loss of gamma-catenin was observed. In six invasive lobular carcinomas, expression of both E-cadherin and catenins was retained. In none of these carcinomas was an E-cadherin mutation detected. Lobular carcinoma in situ adjacent to invasive lobular carcinoma showed simultaneous loss of E-cadherin and catenins in all the cases studied--remarkably, also, in four cases positive for E-cadherin and catenin expression in the invasive component. These results indicate that simultaneous loss of E-cadherin and alpha-, beta- and gamma-catenin may be an important step in the formation of lobular carcinoma in situ, as a precursor of invasive lobular breast cancer. Events additional to E-cadherin inactivation must be involved in the transition of lobular carcinoma in situ to invasive lobular carcinoma.
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PMID:Simultaneous loss of E-cadherin and catenins in invasive lobular breast cancer and lobular carcinoma in situ. 949 56

Leukemia cells (K562) that grow as non-adhesive single cells and have no endogenous cadherin were transfected with an E-cadherin expression vector, and cell clones stably expressing E-cadherin on their surface were established. The expression of E-cadherin induced the up-regulation of catenins, and E-cadherin became associated with catenins. The transfected cells grew as floating aggregates. Cell aggregation was Ca2+-dependent and was inhibited by E-cadherin antibodies. The aggregates dissociated into single cells on the addition of pervanadate. Pervanadate caused a dramatic augmentation of the phosphorylation of E-cadherin, beta-catenin, and gamma-catenin (plakoglobin), but alpha-catenin was not detectably phosphorylated. After pervanadate treatment, beta-catenin and gamma-catenin migrated more slowly on gel electrophoresis, suggesting changes in their conformations due to eventual changes in their phosphorylation levels. In the treated cells, a significant amount of alpha-catenin was dissociated from the E-cadherin.catenin complex. Aggregates of cells expressing an E-cadherin chimeric molecule covalently linked with alpha-catenin were not dissociated on pervanadate treatment, supporting the idea that the dissociation of alpha-catenin from the complex underlies the observed E-cadherin dysfunction.
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PMID:Altered cell adhesion activity by pervanadate due to the dissociation of alpha-catenin from the E-cadherin.catenin complex. 949 37

Alterations in the expression or function of molecules that affect cellular adhesion and proliferation are thought to be critical events for tumor progression. Loss of expression of the cell adhesion molecule E-cadherin and increased expression of the epidermal growth factor receptor are two prominent molecular events that are associated with tumorigenesis. The regulation of E-cadherin-dependent cell adhesion by epidermal growth factor (EGF) was therefore examined in the human breast cancer cell line, MDA-MB-468. In this study, changes were observed in the subcellular distribution of components that mediate the cytoplasmic connection between E-cadherin and the actin-based cytoskeleton in response to activation of the EGF receptor. Serum withdrawal activated E-cadherin-dependent cell-cell aggregation in MDA-MB-468 cells, and this treatment stimulated the interaction of actin, alpha-actinin, and vinculin with E-cadherin complexes, despite the absence of alpha-catenin in these cells. By contrast, the co-precipitation of actin with E-cadherin was not detected in several alpha-catenin positive epithelial cell lines. Treatment with EGF inhibited cellular aggregation but did not affect either the levels of E-cadherin or catenin expression nor the association of catenins (beta-catenin, plakoglobin/gamma-catenin, or p120(cas)) with E-cadherin. However, EGF treatment of the MDA-MB-468 cell line dissociated actin, alpha-actinin, and vinculin from the E-cadherin-catenin complex, and this coincided with a robust phosphorylation of beta-catenin, plakoglobin/gamma-catenin, and p120(cas) on tyrosine residues. Furthermore, inactivation of the EGF receptor in serum-treated MDA-MB-468 cells with either a function-blocking antibody or EGF receptor kinase inhibitors mimicked the effects of serum starvation by stimulating both cellular aggregation and assembly of E-cadherin complexes with vinculin and actin. These results demonstrate that the EGF receptor directly regulates cell-cell adhesion through modulation of the interaction of E-cadherin with the actin cytoskeleton and thus substantiates the coordinate role of both of these molecules in tumor progression and metastasis.
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PMID:The epidermal growth factor receptor modulates the interaction of E-cadherin with the actin cytoskeleton. 953 96

The Wnt signalling pathway is central to normal brain development in vertebrates and invertebrates and mediates cell fate determination, cell adhesion and cell proliferation. However, its relevance to disorders of cerebral development in man is untested. We evaluated the potential involvement of the Wnt signalling pathway in schizophrenia, a disorder of neurodevelopment origin in which alterations in neuronal lamination and orientation have been described. Using immunohistochemistry and semi-quantitative rating scales, we examined the distribution of two components of the Wnt signalling pathway, beta-catenin and gamma-catenin in the hippocampus and subiculum of 12 schizophrenic (DSMIIR criteria) and 14 control subjects. Both catenins were distributed as intraneuronal diffuse and/or ring shaped forms. The diffuse staining of both forms catenin were reduced in the CA3 and beta-catenin was also reduced in the CA4 hippocampal subregion among schizophrenic subjects. These alternations may represent the basis of the developmental brain abnormalities found in schizophrenia and would have functionally important consequences in the adult.
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PMID:Abnormalities of Wnt signalling in schizophrenia--evidence for neurodevelopmental abnormality. 963 33

Cadherins are Ca2+-dependent cell-cell adhesion molecules, and are involved in the formation and maintenance of the histo-architecture. Using a combination of biochemical and immunohistochemical methods, we analyzed the expression of the cadherin-catenin complex in 34 human hepatocellular carcinomas. Unexpectedly, we found the expression of N (neural)-cadherin in normal hepatocytes and all hepatocellular carcinomas examined. In 18 cases, the decreased expression of E (epithelial)-cadherin was observed. Among them, the decreased expression of alpha-catenin and gamma-catenin (plakoglobin) was also observed in 9 and 6 cases, respectively. Thus the decreased expression of alpha-catenin and gamma-catenin was apparently preceded by the decreased expression of E-cadherin. The decreased expression of beta-catenin was not observed in any of the cases analyzed. beta-Catenin was found to accumulate in the cytoplasm of hepatocellular carcinomas with the decreased expression of E-cadherin, despite the presence of N-cadherin at the cell-cell contacts. These results suggest a pivotal role of E-cadherin in the intracellular distribution of catenins in hepatocellular carcinomas.
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PMID:E-cadherin but not N-cadherin expression is correlated with the intracellular distribution of catenins in human hepatocellular carcinomas. 968 18

E-cadherin, the epithelium-specific cadherin, is known to play a major role in tumor progression in many human carcinomas, via intercellular homophilic Ca2+-dependent adhesion. This adhesion is mediated by a group of cytoplasmic proteins, including the alpha-, beta- and gamma-catenins that link the E-cadherin to the actin cytoskeleton. Recent studies have shown that loss or reduction of either E-cadherin or catenin expression was strictly related to clinicopathological data in bladder tumors, and E-cadherin might constitute prognostic factors in bladder carcinogenesis. Here we continued a preliminary work on E-cadherin in bladder cancer. In an effort to evaluate their possible prognostic value, we investigated both E-cadherin and catenins in 99 bladder tumors by immunohistochemistry. E-cadherin and all the catenins were strongly expressed in normal urothelium. Regarding histopathological data, the tumors examined showed that the disrupted expression of each molecule, except for gamma-catenin, was directly related to increasing tumor grade (mainly for alpha- and beta-catenin) and deep invasion (p < or = 0.01). The aberrant expression of E-cadherin and beta-catenin was also correlated to the presence of distant metastasis (p < 0.05). However, only abnormal expression of a-catenin was associated with poor survival (p = 0.037). Therefore our results suggest that alpha-catenin is directly involved in tumor invasion and dedifferentiation and is the only protein of any prognostic value, albeit low in patients with bladder cancer.
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PMID:Expression of E-cadherin and alpha-,beta- and gamma-catenins in human bladder carcinomas: are they good prognostic factors? 970 39


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