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)

Rat 3Y1 cells acquire metastatic potential when transformed with v-src, and this potential is enhanced by double transformation with v-src and v-fos (Taniguchi, S., T. Kawano, T. Mitsudomi, G. Kimura, and T. Baba. 1986. Jpn. J. Cancer Res. 77:1193-1197). We compared the activity of cadherin cell adhesion molecules of normal 3Y1 cells with that of v-src transformed (SR3Y1) and v-src and v-fos double transformed (fosSR3Y1) 3Y1 cells. These cells expressed similar amounts of P-cadherin, and showed similar rates of cadherin-mediated aggregation under suspended conditions. However, the aggregates or colonies of these cells were morphologically distinct. Normal 3Y1 cells formed compacted aggregates in which cells are firmly connected with each other, whereas the transformed cells were more loosely associated, and could freely migrate out of the colonies. Overexpression of exogenous E-cadherin in these transformed cells had no significant effect on their adhesive properties. We then found that herbimycin A, a tyrosine kinase inhibitor, induced tighter cell-cell associations in the aggregates of the transformed cells. In contrast, vanadate, a tyrosine phosphatase inhibitor, inhibited the cadherin-mediated aggregation of SR3Y1 and fosSR3Y1 cells but had little effect on that of normal 3Y1 cells. These results suggest that v-src-mediated tyrosine phosphorylation perturbs cadherin function directly or indirectly, and the inhibition of tyrosine phosphorylation restores cadherin action to the normal state. We next studied tyrosine phosphorylation on cadherins and the cadherin-associated proteins, catenins. While similar amounts of catenins were expressed in all of these cells, the 98-kD catenin was strongly tyrosine phosphorylated only in SR3Y1 and fosSR3Y1 cells. Cadherins were also weakly tyrosine phosphorylated only in the transformed cells. The tyrosine phosphorylation of these proteins was enhanced by vanadate, and inhibited by herbimycin A. Thus, the tyrosine phosphorylation of the cadherin-catenin system itself might affect its function, causing instable cell-cell adhesion.
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PMID:Cadherin-mediated cell-cell adhesion is perturbed by v-src tyrosine phosphorylation in metastatic fibroblasts. 163 52

Alterations in intercellular junction and membrane cytoskeletal proteins may underlie some of the morphological, invasive and metastatic properties of cancer. E-cadherin, a transmembrane protein that functions in epithelial cell-cell interactions at adherens junctions, is linked to the membrane cytoskeletal matrix through interactions with alpha- and beta-catenin. We have carried out studies of E-cadherin and alpha- and beta-catenin in 18 breast cancer cell lines to determine the prevalence and nature of alterations in these genes in breast cancer. Ten lines failed to express E-cadherin protein at detectable levels and seven failed to produce detectable levels of E-cadherin transcripts. In a line lacking E-cadherin expression (SK-BR-3) a homozygous deletion of a large portion of the E-cadherin gene was noted. Localized sequence alterations in E-cadherin transcripts were not identified in any lines. In contrast to the results of a previous study, no relationship was identified between E-cadherin expression and HER-2/NEU expression. Two of the 18 lines had no detectable alpha-catenin protein and six others had reduced levels. The two lines lacking alpha-catenin protein had reduced or undetectable levels of alpha-catenin transcripts, while no consistent changes in alpha-catenin transcript levels were seen in the lines with reduced, but detectable, levels of alpha-catenin protein. Similarly, although two lines lacked beta-catenin protein, in most lines the levels of beta-catenin transcripts and protein were not well correlated with one another. Our findings suggest that alterations in E-cadherin and alpha- and beta-catenin expression are frequent in human breast cancer-derived cell lines, and that in some cases the decreased expression may result from mutations in the genes. Furthermore, the frequent alterations in the expression of these proteins argue that loss of function in the E-cadherin-catenin pathway may be critical in the development of many breast cancers.
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PMID:Frequent alterations in E-cadherin and alpha- and beta-catenin expression in human breast cancer cell lines. 747 52

Loss of epithelioid organization in carcinoma cell lines has been related to invasiveness and poor differentiation of tumors. We investigated the invasion in vitro of various human colon cancer cell lines. Most cell lines were noninvasive into chick heart fragments, and this correlated with an epithelioid morphotype. Only cell lines COLO320DM, SW620, and variants of HCT-8 and DLD-1 were invasive and nonepithelioid. We examined in these cell lines whether invasiveness was related to changes in the structure and function of the E-cadherin/catenin complex. E-cadherin functions as an invasion suppressor and as a cell-cell adhesion molecule when linked to the cytoskeleton via alpha-catenin plus beta- or gamma-catenin. All noninvasive cell lines showed E-cadherin linked to these catenins. The E-cadherin-dependent cell-cell adhesion function in these cell lines was demonstrated by two assays in vitro. It was interesting that all invasive cell lines showed a dysfunctional E-cadherin/catenin complex. COLO320DM, SW480, and SW620 cells were defective in E-cadherin expression, whereas the invasive variants of HCT-8 and DLD-1 lacked the alpha-catenin protein. From clonal epithelioid HCT-8 cultures with functional E-cadherin/catenin complexes, we subcloned, repeatedly, round cell variants that were again invasive and expressed no alpha-catenin protein. Our data suggest that reproducible transformations toward a more invasive phenotype in HCT-8 cells are associated with down-regulation of alpha-catenin. The mechanisms of this transformation and the level of alpha-catenin down-regulation are currently investigated.
Cancer Res 1995 Oct 15
PMID:Transition from the noninvasive to the invasive phenotype and loss of alpha-catenin in human colon cancer cells. 755 55

A number of genetic changes have been documented in prostate cancer, ranging from allelic loss to point mutations and changes in DNA methylation patterns (summarized in Fig. 1). The most consistent changes seen are those of allelic loss events, with the majority of tumours examined showing loss of alleles from at least one chromosomal arm. The short arm of chromosome 8, followed by the long arm of chromosome 16, seem to be the most frequent regions of loss, suggesting the presence of novel tumour suppressor genes. Deletions of one copy of the RB and TP53 genes are less frequent as are mutations of the TP53 gene, and accumulating evidence suggests the presence of an additional tumour suppressor gene on chromosome 17p, which is frequently inactivated in prostate cancer. Alterations in the E-cadherin/alpha catenin mediated cell-cell adhesion mechanism appear to be present in almost half of all prostate cancers and may be critical to the acquisition of metastatic potential of aggressive prostate cancers. Finally, altered DNA methylation patterns have been found in the majority of prostate cancers examined, suggesting widespread alterations in methylation modulated gene expression. The presence of multiple changes in these tumours is consistent with the multistep nature of the transformation process. Finally, efforts to identify prostate cancer susceptibility loci are under way, which may elucidate critical early events in prostatic carcinogenesis.
Cancer Surv 1995
PMID:Molecular biology of prostate cancer progression. 762 57

Association of the c-erbB-2 oncogene product with the cadherin-catenin complex has been demonstrated in human cancer cell lines. Although beta-catenin and plakoglobin have been proven to be crucial for the association, no previous study has shown whether the interactions are direct or indirect. In the present study, the c-erbB-2 gene product was shown by far-Western blotting analysis to associate directly with both beta-catenin and plakoglobin through its cytoplasmic domain core region, which showed extensive homology with epidermal growth factor receptor. These data suggest that c-erbB-2-induced signaling is also directly liked to the cadherin-mediated cell adhesion and "invasion-suppressor" system through beta-catenin and plakoglobin in cancers.
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PMID:c-erbB-2 gene product directly associates with beta-catenin and plakoglobin. 770 5

Genetic characteristics of scirrhous gastric carcinomas are overviewed. Scirrhous carcinomas of the stomach frequently show amplification of c-met and K-sam oncogenes as well as overexpression of 6.0 kb c-met abnormal transcript. For the formation of productive fibrosis and the diffuse infiltrative growth pattern of this malignancy, the essential factors would be not only the loss of cell adhesion molecule function through depressed expression or loss of cadherin or catenin, but also the synchronous overexpression of growth factors from the cancer cells including TGF-beta, PDGF, IGF-II and basic FGF with intimate cancer-stromal interaction through paracrine loop of IL-1 alpha/HGF system.
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PMID:[Genetic characteristics of scirrhous gastric carcinomas]. 794 79

Cadherin cell adhesion molecules play an essential role in creating tight intercellular association and are considered to work as an invasion suppressor system of cancer cells. They form a molecular complex with catenins, a group of cytoplasmic proteins including alpha- and beta-catenins. While alpha-catenin has been demonstrated to be crucial for cadherin function, the role of beta-catenin is not yet fully understood. In this study, we analyzed the cadherin-catenin system in two human cell lines, HSC-39 and its putative subline HSC-40A, derived from a signet ring cell carcinoma of stomach. These cells grow as loose aggregates or single cells, suggesting that their cadherin system is not functional. In these cell lines, an identical 321-base pair in-frame mRNA deletion of beta-catenin was identified; this led to a 107-amino-acid deletion in the NH2-terminal region of the protein. Southern blot analysis disclosed a homozygous deletion in part of the beta-catenin gene. On the other hand, these cells expressed E-cadherin, alpha-catenin, and plakoglobin of normal size. Immunoprecipitation analyses showed that E-cadherin was coprecipitated with the mutated beta-catenin but not with alpha-catenin, and antibodies against beta-catenin did not copurify alpha-catenin. However, the recombinant fusion protein containing wild-type beta-catenin precipitated alpha-catenin from these cells. These results suggest that the dysfunction of E-cadherin in these cell lines is due primarily to its failure to interact with alpha-catenin, and that this defect results from the mutation in beta-catenin. Thus, it is most likely that the association between E-cadherin and alpha-catenin is mediated by beta-catenin, and that this process is blocked by NH2-terminal deletion in beta-catenin. These findings indicate that genetic abnormality of beta-catenin is one of the mechanisms responsible for loosening of cell-cell contact, and may be involved in enhancement of tumor invasion in human cancers.
Cancer Res 1994 Dec 01
PMID:A truncated beta-catenin disrupts the interaction between E-cadherin and alpha-catenin: a cause of loss of intercellular adhesiveness in human cancer cell lines. 795 78

Phosphorylation of beta-catenin, an intracytoplasmic cadherin-binding protein, causes disruption of the cadherin-mediated cell adhesion system in cancer cells. A 185-kDa phosphorylated protein, identified as the c-erbB-2 gene product, was co-immunoprecipitated with the E-cadherin-catenin complex. Association of the c-erbB-2 gene product with the cadherin-catenin complex was proven to be mediated through beta-catenin and plakoglobin using an in vitro protein-protein precipitation system. These results indicate that the c-erbB-2 gene product associates with catenins and may regulate the cell adhesion and invasive growth of cancer.
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PMID:c-erbB-2 gene product associates with catenins in human cancer cells. 799 5

Because the cell adhesion molecule epithelial cadherin (E-cadherin) is absent in many invasive carcinomas, we transfected the E-cadherin gene into E-cadherin-negative, invasive breast cancer cell lines BT549 and HS578t to investigate the role of E-cadherin in invasive behavior. Although the transfected E-cadherin could mediate calcium-dependent aggregation to E-cadherin-transfected L-cells, morphology and invasiveness of the breast cancer cells were not altered. We investigated the strength of the linkage of the transfected E-cadherin to the actin cytoskeleton by examining the Triton X-100 solubility of the transfected E-cadherin. In BT549 and HS578t cells, a large proportion of the transfected E-cadherin was Triton soluble, whereas in E-cadherin-positive MCF-7 cells, Triton-insoluble E-cadherin was apparent at cell-cell borders. Interaction of E-cadherin with the actin cytoskeleton is thought to be mediated by the E-cadherin-binding proteins alpha-catenin, beta-catenin, and plakoglobin. We found normal levels of alpha-catenin and beta-catenin in BT549 and HS578t cells; however, low levels of plakoglobin were expressed in these cells compared to those found in weakly invasive MCF-7 cells. Furthermore, levels of tyrosine phosphorylation of beta-catenin were elevated in E-cadherin-transfected BT549 and HS578t cells compared to MCF-7 cells. We conclude that other factors such as the expression and appropriate posttranslational modification of cadherin-associated proteins must be in place for E-cadherin to be fully functional, i.e., to alter invasiveness. During cancer progression, loss of E-cadherin expression itself or multiple other mechanisms that lead to loss of cell-cell adhesion (mutation, loss of catenin expression, alterations in phosphorylation) may contribute to a more metastatic phenotype.
Cancer Res 1994 Jul 01
PMID:Alterations in beta-catenin phosphorylation and plakoglobin expression in human breast cancer cells. 801 79

Invasion is the cause of cancer malignancy. Invasion leads to metastasis and metastases turn cancer into an incurable disease. The only model of "true" invasion and metastasis is the natural human or animal tumor. Nevertheless, experimental models have largely contributed to the development of new concepts such as the multistep invasion process of metastasis, the growth-separate-from-invasion concept and the transient expression of the invasive phenotype by a subpopulation of cancer cells. All these aspects of invasion are considered within micro-ecosystems that are initiated by the cancer cells but in which host cells may play an equally important role. It is our opinion that invasion is regulated by the balance between the activation and inactivation of two sets of genes, invasion-promoter and invasion-suppressor genes. These genes encode molecules that determine the expression of the invasive and the noninvasive (normal) phenotype. E-cadherin is an invasion-suppressor gene product that belongs to the calcium-dependent homophilic cell-cell adhesion molecules. This transmembrane glycoprotein is involved not only in the mechanics of adhesion but also serves as a signal-transducer via its linkage with the catenins and the actin cytoskeleton. In human and in experimental cancers disturbance of the cadherin-catenin complex have been found at multiple levels. Candidate invasion-promoter molecules may be found among lytic enzymes and their associated molecules, motility factors and heterotypic cell-cell adhesion molecules. Investigation of the cellular interactions within the micro-ecosystem of bone metastasis has lead to the treatment of bone metastases with bisphosphonates. This application demonstrates the potential clinical benefit of a better understanding of the cellular and molecular mechanisms of cancer invasion and metastasis.
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PMID:[When and why does cancer metastasize? An overview of current viewpoints OF the molecular mechanism of invasiveness]. 804 67


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