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 cell adhesion molecule, epithelial cadherin (E-CD) and its binding proteins, alpha- and beta-catenins, in normal liver, chronic liver diseases, and hepatocellular carcinomas (HCCs) was investigated immunohistologically. In normal liver, weak immunostaining of E-CD and catenins was observed at the lateral membranes of the hepatocytes, whereas at the interlobular bile duct epithelia, they stained strongly. No immunoreactions were seen in sinusoidal Kupffer cells. Similar results were observed in the majority of livers from chronic hepatitis and cirrhosis sufferers; however, hepatocytes undergoing regeneration and rosette formation, as well as Hering canals and proliferating ductules, showed markedly increased molecular expression. Analysis of 66 HCC lesions revealed that the majority (64.3-96.6%) of thin trabecular- and pseudoglandular-type tumors preserved or overexpressed E-CD and catenins, whereas thick trabecular-type HCCs frequently showed low E-CD and alpha-catenin expression (56.5-65.2% reduction), suggesting that the thick trabecular histology represented diffuse tumor cell growth. Likewise, the E-CD and catenin expression levels correlated with the HCC cell differentiation grades. These collective results indicate that intercellular adhesion mediated by the E-CD-catenin system plays a role in morphological changes in nonmalignant and malignant hepatic diseases.
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PMID:Expression of epithelial cadherin and alpha- and beta-catenins in nontumoral livers and hepatocellular carcinomas. 867 62

The human papillomavirus type 16 (HPV-16), the type most often associated with cervical cancer, immortalizes primary keratinocytes and inhibits serum/calcium-stimulated differentiation in culture. In this study, we have used a model of keratinocyte immortalization based upon HPV-16 to analyze perturbation of function and expression of E-cadherin, a Ca(2+)-dependent cell-cell adhesion molecule expressed by normal keratinocytes, and its associated proteins. An immortalized keratinocyte cell line generated by cotransfection with HPV-16 E6 and E7 showed decreased membrane E-cadherin expression and redistribution of alpha-, beta-, and gamma-catenin from the undercoat membrane to the cytoplasm. No changes in the level of expression were seen. Selection of the immortalized keratinocyte cell line for resistance to differentiation generated a more transformed cell line with an invasive phenotype, down-regulated E-cadherin and alpha-catenin, and up-regulated the epidermal growth factor receptor (EGFr). Transfection of an E-cadherin expression construct into the differentiation-resistant cell line restored membrane-bound E-cadherin and catenin expression, down-regulated the EGFr, and reversed the invasive phenotype. These results indicate that overexpression of the EGFr correlates with perturbation of the E-cadherin/catenin complex seen in the HPV-16 E6- and E7-transfected keratinocytes and may underlie a functional interaction between growth-regulatory factors and adhesion molecules (E-cadherin/catenin).
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PMID:E-cadherin transfection down-regulates the epidermal growth factor receptor and reverses the invasive phenotype of human papilloma virus-transfected keratinocytes. 891 70

The cell-cell adhesion molecule N-cadherin strongly promotes neurite outgrowth in cultured retinal neurons. To test whether cadherins regulate process outgrowth in retinal neurons in vivo, we have blocked cadherin function in single cells by expression of a dominant negative N-cadherin mutant. We report that when cadherin function is inhibited, axon and dendrite outgrowth are severely impaired, particularly in retinal ganglion cells. Laminar migration and cell type specification, by contrast, appear unaffected. Further, expression of the catenin-binding domain of N-cadherin, which blocks cadherin-mediated adhesion in early embryos, does not affect axon outgrowth, suggesting that outgrowth and adhesion are mediated by distinct regions of the cytoplasmic domain. These findings indicate that cadherins play an essential role in the initiation and extension of axons from retinal ganglion cells in vivo.
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PMID:Cadherin function is required for axon outgrowth in retinal ganglion cells in vivo. 893 17

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

Trophectoderm epithelium formation, the first visible differentiation process during mouse embryonic development, is affected in embryos lacking the cell adhesion molecule E-cadherin. Here we analyze the developmental potential of such E-cadherin-negative embryos, focusing on the organization of cell junctions and the cytoskeleton. To do this we used antibodies directed against alpha-, beta-, or gamma-(plakoglobin)-catenin and junctional and cytoskeletal proteins including ZO-1 and occludin (tight junctions), desmoglein1 (desmosomes), connexin43 (gap junctions), and EndoA (cytokeratin intermediate filaments). Membrane localization of alpha- and beta-catenin, and ZO-1, as well as cortical actin filament organization were abnormal in E-cadherin-negative embryos, and the expression levels of alpha- and beta-catenin were dramatically reduced, all suggesting a regulatory role for E-cadherin in forming the cadherin-catenin complex. In contrast, the membrane localization of plakoglobin, occludin, desmoglein1, connexin43, and cytokeratin filaments appeared unaltered. The unusual morphogenesis in E-cadherin-negative embryos apparently reflects defects in the molecular architecture of a supermolecular assembly involving zonulae adherens, tight junctions, and cortical actin filament organization, although the individual structures still appeared normal in electron microscopical analysis.
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PMID:Cell-junctional and cytoskeletal organization in mouse blastocysts lacking E-cadherin. 918 87

Intestinal trefoil factor (TFF3) is a member of the trefoil family of peptides, which are constitutively expressed in the gastrointestinal tract. TFF3 has been shown to promote migration of intestinal epithelial cells in vitro and to enhance epithelial restitution in vivo. In the present study, we show that the stimulatory effect of TFF3 on the migration of HT29 colonic carcinoma cells requires the perturbation of E-cadherin function, a calcium-dependent cell-cell adhesion molecule in epithelia. A rapid (< 1 minute) and specific tyrosine phosphorylation of beta-catenin and epidermal growth factor receptor was detected in cells treated with recombinant rat TFF3. No phosphorylation of E-cadherin or alpha-catenin was detected. Tyrosine phosphorylation of beta-catenin was associated with reduced membranous E-cadherin expression, perturbation of intercellular adhesion, and promotion of cell motility. These results suggest that TFF3 enhances cell migration through modulation of E-cadherin/catenin complex function. Tyrosine phosphorylation of beta-catenin and epidermal growth factor receptor seems to be involved in this process.
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PMID:Phosphorylation of beta-catenin and epidermal growth factor receptor by intestinal trefoil factor. 942 92

The translational movement of E-cadherin, a calcium-dependent cell-cell adhesion molecule in the plasma membrane in epithelial cells, and the mechanism of its regulation were studied using single particle tracking (SPT) and optical tweezers (OT). The wild type (Wild) and three types of artificial cytoplasmic mutants of E-cadherin were expressed in L-cells, and their movements were compared. Two mutants were E-cadherins that had deletions in the COOH terminus and lost the catenin-binding site(s) in the COOH terminus, with remaining 116 and 21 amino acids in the cytoplasmic domain (versus 152 amino acids for Wild); these are called Catenin-minus and Short-tailed in this paper, respectively. The third mutant, called Fusion, is a fusion protein between E-cadherin without the catenin-binding site and alpha-catenin without its NH2-terminal half. These cadherins were labeled with 40-nm phi colloidal gold or 210-nm phi latex particles via a monoclonal antibody to the extracellular domain of E-cadherin for SPT or OT experiments, respectively. E-cadherin on the dorsal cell surface (outside the cell-cell contact region) was investigated. Catenin-minus and Short-tailed could be dragged an average of 1.1 and 1.8 micron by OT (trapping force of 0.8 pN), and exhibited average microscopic diffusion coefficients (Dmicro) of 1.2 x 10(-10) and 2.1 x 10(-10) cm2/s, respectively. Approximately 40% of Wild, Catenin-minus, and Short-tailed exhibited confined-type diffusion. The confinement area was 0.13 micron2 for Wild and Catenin-minus, while that for Short-tailed was greater by a factor of four. In contrast, Fusion could be dragged an average of only 140 nm by OT. Average Dmicro for Fusion measured by SPT was small (0.2 x 10(-10) cm2/s). These results suggest that Fusion was bound to the cytoskeleton. Wild consists of two populations; about half behaves like Catenin- minus, and the other half behaves like Fusion. It is concluded that the movements of the wild-type E-cadherin in the plasma membrane are regulated via the cytoplasmic domain by (a) tethering to actin filaments through catenin(s) (like Fusion) and (b) a corralling effect of the network of the membrane skeleton (like Catenin-minus). The effective spring constants of the membrane skeleton that contribute to the tethering and corralling effects as measured by the dragging experiments were 30 and 5 pN/micron, respectively, indicating a difference in the skeletal structures that produce these two effects.
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PMID:Cytoplasmic regulation of the movement of E-cadherin on the free cell surface as studied by optical tweezers and single particle tracking: corralling and tethering by the membrane skeleton. 949 Jul 34

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

E-cadherin is the major cell-cell adhesion molecule expressed by epithelial cells. Cadherins form a complex with three cytoplasmic proteins, alpha-, beta-, and gamma-catenin, and the interaction between them is crucial for anchoring the actin cytoskeleton to the intercellular adherens junctions. The invasive behavior of cancer cells has been attributed to a dysfunction of these molecules. In this study, we examined the distribution of the cadherin-catenin complex in a Chinese human thyroid cancer cell line, CGTH W-2, compared with that in normal human thyroid epithelial cells. In the normal cells, using immunofluorescence staining, E-cadherin and alpha-, beta-, and gammm-catenin were found to be localized at the intercellular junction and appeared as 135, 102, 90, and 80 kD proteins on Western blots. In CGTH W-2 cells, no E-cadherin and gamma-catenin immunoreactivity was detected by immunofluorescence or Western blotting; alpha- and beta-catenin were detected as 102 and 90 kD proteins on blots but gave a diffuse cytoplasmic immunofluorescence staining pattern in most cells, while beta-catenin was also distributed throughout the cytoplasm in most cells but was found at the cell junction in some, where it colocalized with alpha-actinin. The present data indicate that the loss of cell adhesiveness in these cancer cells may be due to incomplete assembly of the cadherin-catenin complex at the cell junction. However, this defect did not affect the linkage of actin bundles to vinculin-enriched intercellular junctions.
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PMID:Distribution of the cadherin-catenin complex in normal human thyroid epithelium and a thyroid carcinoma cell line. 970 70

Somitogenesis during early stages in the chick and mouse embryo was examined in relation to N-cadherin-mediated adhesion. Previous studies indicated that N-cadherin localizes to the somite regions during their formation. Those observations were extended to include a spatiotemporal immunohistochemical analyses of beta-catenin and alpha-catenin, as well as a more detailed study of N-cadherin, during segmentation, compaction, and compartmentalization of the somite. N-cadherin and the catenins appear early within the segmental plate and are expressed as small patch-like foci throughout this tissue. The small foci of immunostaining coalesce into larger clusters of N-cadherin/catenin-expressing regions. The clusters subsequently coalesce into a region of centrally localized cells that express N-cadherin/catenins at their apical surfaces. The multiple clusters are spaced wide apart in the anterior segmental plates that form the first 6 somite pairs, as contrasted to segmental plates that form somites 7 and beyond. To examine the functional significance of N-cadherin, segmental plates were exposed to antibodies that perturb N-cadherin-mediated adhesion in the chick embryo. The multiple, anomalous somites that result in these experiments indicate that each N-cadherin/catenin-expressing cluster can give rise to a somitic structure. beta-Catenin involvement in somitogenesis suggests a role for Wnt-mediated signaling. Embryos treated with LiCl also show induction of similar anomalous somites indicating further the possibility that Wnt-mediated signaling may be involved in the clustering event. It is suggested that beta-catenin serves to initiate the adhesion process which is spread then by N-cadherin. Later during compartmentalization, N-cadherin/catenins remain expressed by the myotome compartment. Taken together, these results suggest that the Ca2+-dependent cell adhesion molecule N-cadherin and the intracellular catenins are important in segmentation and formation of the somite and myotome compartment. It is proposed that the N-cadherin-mediated adhesion process may serve as a common, evolutionarily conserved, link in the differentiation pathways of skeletal and cardiac muscle.
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PMID:N-cadherin/catenin-mediated morphoregulation of somite formation. 975 5


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