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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 pivotal for the regulation of cancer invasion. It not only serves cell-cell adhesion but also transduces signals from the micro-environment to other molecular complexes possibly implicated in invasion. Both functions are disturbed when the extracellular part of E-cadherin is cleaved off. Moreover, upon release into the environment, the E-cadherin fragments may interfere with intact complexes, as indicated by experiments with His-Ala-Val (HAV)-containing peptides that are homologous to parts of the first extracellular domain of E-cadherin. Scatter factor/hepatocyte growth factor (SF/HGF), on binding to its c-met tyrosine kinase receptor, can induce invasion through tyrosine phosphorylation of beta-catenin. SF/HGF-induced invasion is also associated with phosphorylation of pp125FAK, and both invasion and phosphorylation are inhibited by platelet-activating factor (PAF). Activation of the membrane-bound non-receptor tyrosine kinase pp60src can also induce invasion. Signal transduction pathways starting from pp60src include E-cadherin-associated beta-catenin as well as the focal adhesion kinase pp125FAK. Whereas all invasion-inducing pathways implicate phosphoinositide 3-kinase, the PAF pathway seems to be E-cadherin-catenin-independent. We conclude that cancer cell invasion is regulated by paracrine and autocrine factors that are released upon cross-talk with the host cells.
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PMID:Extracellular regulation of cancer invasion: the E-cadherin-catenin and other pathways. 1032 Sep 32

Tumour cell metastatic potential is significantly enhanced following treatment with HGF/SF, the ligand for the c-met receptor tyrosine kinase. Following c-met activation in tumour cells, phosphorylation of beta-catenin occurs, together with loss of intercellular adhesion and a gain in the motile and invasive nature of the cell. In this study we show that c-met is co-localised with beta-catenin and E-cadherin at regions of cell-cell contact in human colon cancer (HRT18 and HT115) and two breast cancer (MCF7 and MDA MB 231) cell lines. Immunoprecipitation studies demonstrated an association between c-met and members of the cadherin adhesion complex in these epithelial tumour cells, along with the membrane tyrosine protein phophatase, PTPmu. We conclude that the HGF/SF receptor, c-met, together with members of the cadherin/catenin cell-cell adhesion system and PTPmu, may form part of a protein complex in E-cadherin positive tumour cells that acts to regulate intercellular adhesion following HGF/SF stimulation.
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PMID:Association of the HGF/SF receptor, c-met, with the cell-surface adhesion molecule, E-cadherin, and catenins in human tumor cells. 1042 98

In recent years developmental biology has contributed a great deal to cancer research. This is in part because both fields address the question of how genes control the three-dimensional organisation of tissues, and how mutation of genes alters this. But also in recent years, the discovery that signalling pathways are conserved from worms to man, combined with the power of developmental biology's model organisms, principally Drosophila and C. elegans, to reveal signalling pathways that control tissue growth and organisation, has had a huge impact. Examples of this are the subject of the reviews in this issue, including the EGF-receptor, Wnt/APC/catenin, TGF-beta/Smad and hedgehog/patched/smoothened pathways, all of which were discovered and/or pieced together in model organisms, and all of which are disrupted by mutation in human cancer. Other topics considered are the control and execution of apoptosis; the search for tumour-suppressor-like genes in Drosophila; and genes of the Polycomb and Trithorax Groups that regulate the commitment of cells to patterns of differentiation, and that are among the targets for chromosome translocations. These stories illustrate how developmental biology has shown that there are many more signalling pathways relevant to neoplasia than the receptor tyrosine kinase pathways that first dominated the field; and that the signalling is more than just mitogenic or anti-mitogenic, and should be viewed as providing cells with information about their position and neighbours, that determines their role, differentiation and behaviour.
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PMID:The impact of developmental biology on cancer research: an overview. 1072 82

In C. elegans, lin-7 as well as lin-2/lin-10 is involved in the proper localization of the LET-23 receptor tyrosine kinase that regulates vulval induction. The mammalian homologue, mLin-7, forms a ternary complex with the mammalian homologues of LIN-2 and LIN-10 and localizes at cell-cell junctions in epithelial cells, but the mechanism of this localization of mLin-7 is unknown. Nectin is an immunoglobulin-like cell-cell adhesion molecule that is involved in organization of adherens and tight junctions in epithelial cells. Nectin is indirectly associated with the cadherin-catenin system and the actin cytoskeleton through afadin, an actin filament-binding protein. We showed here that mLin-7 localized at the nectin-based cell-cell junctions. This localization of mLin-7 required the interaction of nectin with afadin, but not the cadherin-catenin system or the actin cytoskeleton. mLin-7 did not directly interact with nectin or afadin. The results indicate that mLin-7 localizes at cell-cell junctions through the nectin-afadin system.
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PMID:Localization of mLin-7 at nectin-based cell-cell junctions. 1197 Nov 89

While searching for potential candidate molecules relevant for the pathogenesis of endometriosis, we discovered a 2910-base pair cDNA encoding a novel putative 411-amino acid integral membrane protein that we called shrew-1. The putative open-reading frame was confirmed with antibodies against shrew-1 peptides that labeled a protein of approximately 48 kDa in extracts of shrew-1 mRNA-positive tissue and also detected ectopically expressed shrew-1. Expression of epitope-tagged shrew-1 in epithelial cells and analysis by surface biotinylation and immunoblots demonstrated that shrew-1 is indeed a transmembrane protein. Shrew-1 is able to target to E-cadherin-mediated adherens junctions and interact with the E-cadherin-catenin complex in polarized MCF7 and Madin-Darby canine kidney cells, but not with the N-cadherin-catenin complex in nonpolarized epithelial cells. Direct interaction of shrew-1 with beta-catenin in in vitro pull-down assay suggests that beta-catenin might be one of the proteins that targets and/or retains shrew-1 in the adherens junctions. Interestingly, shrew-1 was partially translocated in response to scatter factor (ligand of receptor tyrosine kinase c-met) from the plasma membrane to the cytoplasm where it still colocalized with endogenous E-cadherin. In summary, we introduce shrew-1 as a novel component of adherens junctions, interacting with E-cadherin-beta-catenin complexes in polarized epithelial cells.
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PMID:Novel membrane protein shrew-1 targets to cadherin-mediated junctions in polarized epithelial cells. 1459 18

E-cadherin is an essential adhesion protein as well as a tumor suppressor that is silenced in many cancers. Its adhesion-dependent regulation of signaling has not been elucidated. We report that E-cadherin can negatively regulate, in an adhesion-dependent manner, the ligand-dependent activation of divergent classes of receptor tyrosine kinases (RTKs), by inhibiting their ligand-dependent activation in association with decreases in receptor mobility and in ligand-binding affinity. E-cadherin did not regulate a constitutively active mutant RTK (Neu*) or the ligand-dependent activation of LPA receptors or muscarinic receptors, which are two classes of G protein-coupled receptors. EGFR regulation by E-cadherin was associated with complex formation between EGFR and E-cadherin that depended on the extracellular domain of E-cadherin but was independent of beta-catenin binding or p120-catenin binding. Transfection of E-cadherin conferred negative RTK regulation to human melanoma and breast cancer lines with downregulated endogenous E-cadherin. Abrogation of E-cadherin regulation may contribute to the frequent ligand-dependent activation of RTK in tumors.
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PMID:E-cadherin-mediated adhesion inhibits ligand-dependent activation of diverse receptor tyrosine kinases. 1505 84

E-cadherin was originally viewed exclusively as a structural protein mediating cell-cell adhesion. More recently, its signaling functions have been recognized. Loss or downregulation of E-cadherin releases proteins, such as b-catenin and p120 catenin, from a membrane-bound state into the cytoplasm, which are known to regulate transcriptional activity. E-cadherin is known to interact with receptor tyrosine kinases, such as epidermal growth factor receptor (EGFR). However, previously, only the regulation of E-cadherin mediated adhesion through EGFR has been described and activation of EGFR was implicated in loss of cell adhesion, and increased cell migration and invasion. Now, Qian et al. (EMBO J 2004, 23:1739-48) describe that E-cadherin mediated adhesion inhibits receptor tyrosine kinase (RTK) activity. E-cadherin was found to interact through its extracellular domain with EGFR and other receptor tyrosine kinases, thereby decreasing receptor mobility and ligand-affinity. This is a novel mechanism by which E-cadherin inhibits RTKs, and suggests that downregulation of E-cadherin may contribute to the frequently observed activation of RTKs in tumors.
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PMID:No one-way street: cross-talk between e-cadherin and receptor tyrosine kinase (RTK) signaling: a mechanism to regulate RTK activity. 1566 13

Cell-culture studies indicate that tyrosine phosphorylation of the cadherin-catenin-complex (CCC) is one of the post-translational mechanism regulating E-cadherin-mediated cell adhesion. In this investigation, controlled application of a tyrosine phosphatase inhibitor (orthovanadate) and tyrosine kinase inhibitor (tyrphostin) to early Drosophila embryos, followed by biochemical assays and phenotypic analysis, has been utilized to address the mechanism by which tyrosine phosphorylation regulates E-cadherin-mediated cell adhesion in vivo. Our data suggest that, in the Drosophila embryo, beta-catenin (Drosophila homolog Armadillo) is the primary tyrosine-phosphorylated protein in the CCC. The increase in tyrosine phosphorylation correlates with a loss of epithelial integrity and adherens junctions in the ectoderm of early embryos. Late application of the phosphatase inhibitor does not have this effect, presumably because of the formation of septate junctions in late embryos. Co-immunoprecipitation assays have demonstrated that tyrosine hyper-phosphorylation does not cause the dissociation of Drosophila (D)E-cadherin and alpha-catenin or Armadillo, suggesting that abrogation in adhesion is most likely attributable to the detachment of actin-associated proteins from the CCC. Finally, although the Drosophila epidermal growth factor receptor (EGFR), a receptor tyrosine kinase, is linked to the CCC and shows genetic interactions with DE-cadherin, we find that a constitutively active Drosophila EGFR construct does not cause any detectable changes in the level of tyrosine phosphorylation of Armadillo or destabilization of the CCC.
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PMID:Regulation of cell adhesion in the Drosophila embryo by phosphorylation of the cadherin-catenin-complex. 1636 17

Integration of receptor tyrosine kinase, integrin, and cadherin activities is crucial for normal cell growth, motility, and adhesion. Here, we describe roles for p120-catenin (p120) and p190RhoGAP that coordinate crosstalk between these systems and regulate cadherin function. Surprisingly, PDGFR-induced actin remodeling in NIH3T3 cells is blocked in the absence of p120, and the cells are partially transformed via constitutive activation of Rho. We have traced the mechanism to unexpected codependent roles for p120 and p190RhoGAP in regulating Rac-dependent antagonism of Rho. Receptor-induced Rac activity causes translocation of p190RhoGAP to adherens junctions (AJs), where it couples to the cadherin complex via interaction with p120. AJ formation is dependent on this p120-p190RhoGAP interaction and fails altogether if either of these proteins are compromised. We propose that Rac activation links diverse signaling systems to AJ assembly by controlling transient p190RhoGAP interactions with p120 and localized inhibition of Rho.
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PMID:p120-catenin and p190RhoGAP regulate cell-cell adhesion by coordinating antagonism between Rac and Rho. 1712 72

Carcinomas arising from colon epithelia develop or progress in a stromal microenvironment that is elevated in hyaluronan; interactions between elevated hyaluronan and the CD44 receptors on epithelial tumor cells activate an HA-receptor tyrosine kinase-mediated cell survival pathway. In this review we provide evidence that the hyaluronan-ErbB2-PI3kinase/AKT-ss-catenin-COX-2 signaling axis leads to intestinal epithelial and colon tumor cell division and proliferation. This review includes a summary of the authors work over the past years as well as citations of specific reviews related to role of hyaluronan in the pathogenesis of colon cancer.
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PMID:Hyaluronan, CD44, and cyclooxygenase-2 in colon cancer. 1866 47


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