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

Expression of the calcium-dependent adhesion molecule E-cadherin suppresses the invasion of cells in vitro, but the mechanism of this effect is unknown. To investigate this mechanism, we analyzed the effects of expressing E-cadherin in mouse L-cells and rat astrocyte-like WC5 cells. Increased cellular adhesion mediated by E-cadherin reduced invasion in WC5 cells and in some L-cells, but not in others. In all cases, suppression of invasion was correlated with decreased cell movement as assessed in an in vitro wound-filling assay and a transwell motility assay. To define the relationship between adhesion mediated by E-cadherin and suppression of motility, we analyzed the effects of deleting different regions of the E-cadherin cytoplasmic domain. E-cadherin lacking the entire cytoplasmic domain did not mediate calcium-dependent adhesion and did not reduce cell motility when expressed in WC5 cells. E-cadherin lacking a portion of the catenin-binding domain did not associate with the cytoskeleton and did not promote adhesion, yet still suppressed the motility of WC5 cells. In addition, E-cadherin that retains an intact catenin-binding domain, but lacks a juxtamembrane portion of the cytoplasmic domain, mediated effective adhesion, but did not suppress motility. These results indicate E-cadherin mediates adhesion and suppresses cell motility via distinct of E-cadherin plays a key role in suppressing motility.
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PMID:E-cadherin mediates adhesion and suppresses cell motility via distinct mechanisms. 905 87

E-Cadherin has been shown to be an invasion tumor suppressor gene, but few epidemiological studies have revealed relationships between loss of E-cadherin expression and invasive tumor growth and/or metastasis. The adhesive function of E-cadherin is dependent on the integrity of the catenin components which link E-cadherin to the actin filaments. In order to achieve a better correlation between the loss of cell adhesion and metastasis in cancer, we decided to investigate both E-cadherin and the catenins. 157 archival primary mammary carcinomas were immunohistochemically studied using antibodies against E-cadherin, alpha-, beta- and gamma-catenin. The following results were obtained: (a) Independent of the presence of E-cadherin, loss of expression of one or multiple catenins was noted; (b) loss of E-cadherin and alpha-catenin expression was more pronounced in lobular-type than ductal-type carcinomas; c) axillary lymph node metastases were completely lacking only in the group where expression of E-cadherin, alpha- and beta- catenin was preserved: d) no correlation between expression of c-erbB-2 and E-cadherin or one of the catenins was found. The results demonstrate for the first time that consideration of both the expression of E-cadherin and of the three catenins is useful in evaluation of the metastatic potential of mammary carcinomas.
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PMID:Expression of E-cadherin and catenins in invasive mammary carcinomas. 906 80

Current androgen ablation therapies for advanced prostate cancer are not curative. Several recently identified critical biochemical pathways, including the E-cadherin/catenin complex, programmed cell death, telomerase activity, and receptor kinases, may represent targets for new therapeutic approaches. Different forms of gene therapy are also being investigated. Drug development is at the pre-clinical stage, but phase I and II clinical trials are planned, and may lead to a wider choice of therapeutic options for prostate cancer in the not too distant future.
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PMID:New perspectives in the treatment of prostate cancer. 907 7

Cadherins are a family of calcium-dependent cell-cell adhesion molecules involved in cell-cell aggregation and morphoregulatory cell function. Dysfunction of the cadherin pathway is involved in tumour invasiveness and disease progression for a variety of carcinomas. E-cadherin is a prognostic marker in prostatic cancer, based on the correlation of the grade of E-cadherin expression and tumour grade, stage, metastasis and survival, as well as recurrence after radical prostatectomy. P-cadherin was shown to be lost in all prostatic cancers, although this most likely reflects loss of the basal cell population rather than a transcriptional down-regulation, suggesting that loss of P-cadherin expression is an early event in the tumorigenesis of prostatic carcinomas. Catenins, particularly alpha-catenin, also play an important role in the dysfunction of the cell adhesion complex. Mechanisms of inactivation of the cadherin-catenin pathway include LOH, gene deletions and gene promoter hypermethylation. Therapeutic strategies have been investigated in tumour models, i.e. the use of demethylating agents for the hypermethylated promoter region of E-cadherin or gene transfer in PC-3 cells with homozygous deletion of the alpha-catenin gene. The complexity of neoplastic changes cannot be explained by alterations of cell adhesion molecules alone; but as demonstrated, cadherins and catenins play an important role in this process.
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PMID:The cadherin cell-cell adhesion pathway in prostate cancer progression. 908 71

In a recently developed human breast cancer model, treatment of tumor cells in a 3-dimensional culture with inhibitory beta1-integrin antibody or its Fab fragments led to a striking morphological and functional reversion to a normal phenotype. A stimulatory beta1-integrin antibody proved to be ineffective. The newly formed reverted acini re-assembled a basement membrane and re-established E-cadherin-catenin complexes, and re-organized their cytoskeletons. At the same time they downregulated cyclin D1, upregulated p21(cip,wat-1), and stopped growing. Tumor cells treated with the same antibody and injected into nude mice had significantly reduced number and size of tumors in nude mice. The tissue distribution of other integrins was also normalized, suggesting the existence of intimate interactions between the different integrin pathways as well as adherens junctions. On the other hand, nonmalignant cells when treated with either alpha6 or beta4 function altering antibodies continued to grow, and had disorganized colony morphologies resembling the untreated tumor colonies. This shows a significant role of the alpha6/beta4 heterodimer in directing polarity and tissue structure. The observed phenotypes were reversible when the cells were disassociated and the antibodies removed. Our results illustrate that the extracellular matrix and its receptors dictate the phenotype of mammary epithelial cells, and thus in this model system the tissue phenotype is dominant over the cellular genotype.
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PMID:Reversion of the malignant phenotype of human breast cells in three-dimensional culture and in vivo by integrin blocking antibodies. 910 51

alpha-Catenin is a 102-kDa protein exhibiting homology to vincuin, and it forms complexes with cadherins or the tumor-suppressor gene product adenomatous polyposis coli through binding to beta-catenin or plakoglobin (gamma-catenin). The incorporation of alpha-catenin into the cadherin-catenin complexes is a prerequisite for expression of the cell-adhesive activity of cadherins. Using an in vitro assay system involving bacterially expressed proteins, we localized a region in alpha-catenin required for molecular interaction with beta-catenin and plakoglobin. Analysis of various truncated alpha-catenin molecules revealed that amino-terminal residues 48-163 are able to bind to beta-catenin and plakoglobin. Consistent with the observation that beta-catenin and plakoglobin bind to the same region of alpha-catenin, beta-catenin competed with the binding of plakoglobin to alpha-catenin and vice versa. Under the conditions used, beta-catenin bound to alpha-catenin with higher affinity than did plakoglobin. Scatchard analysis indicated that the affinity of the interaction between alpha-catenin and beta-catenin or that between alpha-catenin and plakoglobin was moderately strong (Kd = 3. 8 x 10(-8) and 7.7 x 10(-8), respectively). When transfected into L cells expressing E-cadherin, the amino-terminal region of alpha-catenin (from residue 1 to 226) formed complexes with beta-catenin supporting the in vitro binding experiment results.
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PMID:Identification of the domain of alpha-catenin involved in its association with beta-catenin and plakoglobin (gamma-catenin). 911 Sep 93

Alterations in the E-cadherin-mediated cell-cell adhesion pathway are commonly observed in urologic malignancies. This issue has been addressed most thoroughly in prostate cancer. Whereas both cadherin and catenin dysfunction have been seen in human prostate cancers, only down-regulation of E-cadherin has been shown for bladder cancer and renal-cell carcinoma. Although studies in bladder cancer and renal-cell carcinoma are less mature than studies in prostate cancer, they support the hypothesis that immunostaining for E-cadherin may be of significance for both diagnostic and prognostic purposes. Finally, the E-cadherin-mediated cell-cell adhesion pathway may represent a novel chemotherapeutic target for bladder cancer, prostate cancer, and renal-cell carcinoma. Obviously, more work lies ahead to translate these important observations from the bench to the bedside.
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PMID:The E-cadherin cell-cell adhesion pathway in urologic malignancies. 911 56

Epithelial cells are the most important cell type in the development of human malignancies. More than 90% of all malignant tumors are carcinomas, and thus of epithelial origin. Aberrant growth and the ability to invade the underlying tissues are intrinsic properties of the fatally altered cells. Multiple genetic alterations that can influence growth and genetic stability of the carcinoma cells have been characterised during tumor progression. Loss of epithelial morphology and the acquisition of mesenchymal characteristics are typical for carcinoma cells late in tumor progression and correlate with metastatic potential. In vitro, epithelial-mesenchymal transitions can be induced by interference with the integrity of the adherens junction, by signalling via tyrosine kinases, and by oncogene expression. In carcinoma cells, loss or downregulation of E-cadherin expression are frequently observed in carcinomas, and correlate with the malignancy of the tumor. In general, this change in expression is regulated at the transcriptional level. However, tumor types or cell lines exist which show mesenchymal characteristics but nevertheless express E-cadherin protein or mRNA. A more-detailed analysis demonstrated that other mechanisms that interfere with E-cadherin-mediated cell adhesion can be operative. Mutations in the E-cadherin gene and loss or mutation of the second, intact copy as well as mutation in the catenin genes, which encode proteins that interact with the cytoplasmic portion of E-cadherin, can be observed. In addition, transient or unregulated phosphorylation by receptor tyrosine kinases or oncogenic tyrosine kinases, respectively, can interfere with the epithelial morphology and induce a mesenchymal conversion. Since tyrosine phosphorylation of beta-catenin correlates with the epithelial-mesenchymal transition that is observed, E-cadherin-mediated cell adhesion might be modulated by such a mechanism. Interestingly, the same molecules implicated in the control of malignant properties turn out to play fundamental roles in the control of normal epithelial growth, differentiation and morphogenesis.
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PMID:Epithelial-mesenchymal transitions in cancer progression. 912 38

Reductions in cell-cell adhesion and stromal and vascular invasion are essential steps in the progression from localized malignancy to metastatic disease. In this study, changes in the expression of the components of the E-cadherin-catenin cell adhesion complex have been investigated using immunohistochemical techniques in primary tumours and nodal metastases from 36 patients with squamous cell carcinoma of the head and neck. For 14 patients the corresponding primary and nodal metastases samples were available. None of the 51 samples showed normal E-cadherin expression when compared with either the adjacent normal squamous epithelium or with normal colonic epithelium that was used as positive control material. In 88% of primary tumours fewer than 50% of cells exhibited normal membranous E-cadherin expression. Loss of membranous E-cadherin expression was more extensive in poorly differentiated carcinomas while, in individual carcinomas, membranous E-cadherin expression was stronger in those parts of the neoplasm that expressed the differentiation marker involucrin. Expression of beta-catenin generally paralleled that of E-cadherin, but in 12 cases there was strong membranous beta-catenin expression in samples that exhibited predominantly cytoplasmic E-cadherin labelling. Expression of alpha-catenin was generally weak and did not correlate with the expression of either beta-catenin or E-cadherin. Marked intratumoral heterogeneity for protein expression was evident for all antibodies, and the abnormal expression of the catenins is a novel finding. E-cadherin is expressed more intensely in cells with greater squamous differentiation, but there was no correlation between the decreased expression of any of the adhesion molecules of the E-cadherin complex tested and local recurrence, metastasis or survival. The loss of expression of components of the E-cadherin complex is a common abnormality in squamous carcinomas and, while it may be permissive for metastasis, it does not appear to be the only determinant of this process.
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PMID:Expression of the E-cadherin-catenin cell adhesion complex in primary squamous cell carcinomas of the head and neck and their nodal metastases. 916 40

E-cadherin and its associated cytoplasmic proteins alpha-, beta-, and gamma-catenin and p120 protein play a crucial role in the maintenance of normal tissue architecture. Perturbation in any of these molecules results in loss of intercellular adhesion and cell transformation. In this study, we have used immunohistochemistry to localize E-cadherin, alpha-, beta-, and gamma-catenin, and p120 in paraffin-embedded tissues from 60 patients with colonic polyps. Specimens consisted of 20 samples each from hyperplastic, inflammatory, and sporadic adenomatous polyps. Ten histologically normal colonic samples were also studied. Normal colonic epithelial cells showed strong E-cadherin/ catenin/p120 immunostaining at the cell-cell junction. In 65% (13/20) of adenomatous polyps, beta-catenin showed abnormal nuclear localization with increased expression and loss of membranous staining compared with the adjacent normal mucosa. In two cases (10%), gamma-catenin was seen in the nuclei. Heterogeneous p120 immunoreactivity was observed in four cases (20%), of which two also showed beta-catenin nuclear localization. Preserved membranous alpha-catenin staining was seen in all cases. E-cadherin was down-regulated in 6 of 20 (30%) adenomas with loss of cell surface staining in 3 cases. All hyperplastic and 40% (8/20) of inflammatory polyps showed weak E-cadherin expression on the surface epithelium. Similar changes in p120 expression were seen in all hyperplastic and 20% (4/20) of inflammatory polyps. There were no concomitant changes in alpha-, beta-, or gamma-catenin expression. These results indicate that changes in catenin expression and cellular localization occur early in dysplastic colonic lesions.
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PMID:Expression of E-cadherin-associated molecules (alpha-, beta-, and gamma-catenins and p120) in colorectal polyps. 917 91


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