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)

Rho GTPases are important regulators of cellular behavior through their effects on processes such as cytoskeletal organization. Here we show interactions between Drosophila Rho1 and the adherens junction components alpha-catenin and p120(ctn). We find that while Rho1 protein is present throughout the cell, it accumulates apically, particularly at sites of cadherin-based adherens junctions. Cadherin and catenin localization is disrupted in Rho1 mutants, implicating Rho1 in their regulation. p120(ctn) has recently been suggested to inhibit Rho activity through an unknown mechanism. We find that Rho1 accumulates in response to lowered p120(ctn) activity. Significantly, we find that Rho1 binds directly to alpha-catenin and p120(ctn) in vitro, and these interactions map to distinct surface-exposed regions of the protein not previously assigned functions. In addition, we find that both alpha-catenin and p120(ctn) co-immunoprecipitate with Rho1-containing complexes from embryo lysates. Our observations suggest that alpha-catenin and p120(ctn) are key players in a mechanism of recruiting Rho1 to its sites of action.
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PMID:Rho1 interacts with p120ctn and alpha-catenin, and regulates cadherin-based adherens junction components in Drosophila. 1213 16

Cadherin-catenin complexes, localized to adherens junctions, are essential for cell-cell adhesion. One means of regulating adhesion is through the juxtamembrane domain of the cadherin cytoplasmic tail. This region is the binding site for p120, leading to the hypothesis that p120 is a key regulator of cell adhesion. p120 has also been suggested to regulate the GTPase Rho and to regulate transcription via its binding partner Kaiso. To test these hypothesized functions, we turned to Drosophila, which has only a single p120 family member. It localizes to adherens junctions and binds the juxtamembrane region of DE-cadherin (DE-cad). We generated null alleles of p120 and found that mutants are viable and fertile and have no substantial changes in junction structure or function. However, p120 mutations strongly enhance mutations in the genes encoding DE-cadherin or Armadillo, the beta-catenin homologue. Finally, we examined the localization of p120 during embryogenesis. p120 localizes to adherens junctions, but its localization there is less universal than that of core adherens junction proteins. Together, these data suggest that p120 is an important positive modulator of adhesion but that it is not an essential core component of adherens junctions.
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PMID:Drosophila p120catenin plays a supporting role in cell adhesion but is not an essential adherens junction component. 1255 51

Cell adhesion molecules of the cadherin family contribute to the regulation of cell shape and fate by mediating strong intercellular adhesion through Ca2+-dependent interaction of their ectodomain and association of their cytoplasmic tail to actin. However, the mechanisms co-ordinating cadherinmediated adhesion with the reorganization of the actin cytoskeleton remain elusive. Here, the formation of de novo contacts was dissected by spreading cells on a highly active N-cadherin homophilic ligand. Cells responded to N-cadherin activation by extending lamellipodium and organizing cadherin-catenin complexes and actin filaments in cadherin adhesions. Lamellipodium protrusion, associated with actin polymerization at the leading edge sustained the extension of cadherin contacts through a phosphoinositide 3-kinase (PI 3-kinase)-Rac1 pathway. Cadherin adhesions were formed by PI 3-kinase-independent, Rac1-dependent co-recruitment of adhesion complexes and actin filaments. The expression and localization of p120 at the plasma membrane, associated with an increase in membrane-associated Rac1 was required for both cell responses, consistent with a major role of p120 in signalling pathways initiated by cadherin activation and contributing to Rac1-dependent contact extension and maturation. These results provide additional information on the mechanisms by which cadherin coordinates adhesion with dynamic changes in the cytoskeleton to control cell shape and intercellular junction organization.
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PMID:Lamellipodium extension and cadherin adhesion: two cell responses to cadherin activation relying on distinct signalling pathways. 1465 80

Aging is associated with a loss of renal reserve, and increased sensitivity to either xenobiotic or physiologic insult. Given the critical role of the cadherin/catenin complex in establishing and maintaining the integrity and polarity of tubular epithelial cells, it was hypothesized that aging was associated with alterations in renal cadherin/catenin complexes. Histological assessment of aged (24 months) kidneys harvested from male Fischer 344 rats demonstrates mild degeneration of proximal tubules, multifocal chronic lymphocytic infiltration, moderate development of protein casts inside tubules, and tubular dilatation or degeneration. Western blot analysis revealed that N-cadherin protein expression is not constant over 24 months. N-cadherin expression increased from 4 to 9 months, with peak levels at 9 and 13 months. A decrease in expression was seen at 19 months and an almost complete loss of expression was seen at 24 months. In contrast, the expression of E- and Ksp-cadherin was constant over 24 months. A loss of alpha-catenin at was seen at 19 and 24 months in the absence of changes in beta-, gamma-, and p120-catenin. This pattern of N-cadherin expression (increase followed by decrease) was confirmed by real-time PCR analysis, which demonstrated a similar pattern as the Western blot, suggesting that the loss of N-cadherin protein was due to decreased gene expression. The loss of N-cadherin was specific for the kidney, as no changes in N-cadherin expression in the liver, brain, or testes were seen during aging. The conclusion that loss of N-cadherin expression is a critical component of the renal dysfunction associated with aging is supported by the finding that caloric restriction attenuates the loss of N-cadherin, as well as the finding that a significant loss of N-cadherin is seen in the kidneys of ZDF x SHHF rats, a genetic model of end-stage renal disease. Cadherin and catenin expression was further analyzed by immunofluorescence. A significant loss of staining of both N-cadherin and alpha-catenin was seen in the proximal tubules of rats at 24 months. Interestingly, this corresponded with delocalization of the alpha-1 subunit of the Na+K+-ATPase, i.e. aberrant staining on cell-cell borders and some indication of apical staining in proximal tubules. Taken together, these data suggest that aging is associated with decreased expression of N-cadherin and alpha-catenin and is associated with a loss of cell polarity.
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PMID:Loss of N-cadherin and alpha-catenin in the proximal tubules of aging male Fischer 344 rats. 1517 34

Cadherin-catenin complexes have been well established as key regulators of cell adhesion. Recent work has elucidated a pivotal role for these molecules in synaptic assembly, remodelling and plasticity. Far from being mere adhesive scaffolds, cadherins might directly regulate cell signalling to modulate synaptic connectivity.
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PMID:Cadherins and catenins in synapse development. 1572 47

The E-Cadherin-catenin complex plays a critical role in epithelial cell-cell adhesion, polarization, and morphogenesis. Here, we have analyzed the mechanism of Drosophila E-Cadherin (DE-Cad) localization. Loss of function of the Drosophila exocyst components sec5, sec6, and sec15 in epithelial cells results in DE-Cad accumulation in an enlarged Rab11 recycling endosomal compartment and inhibits DE-Cad delivery to the membrane. Furthermore, Rab11 and Armadillo interact with the exocyst components Sec15 and Sec10, respectively. Our results support a model whereby the exocyst regulates DE-Cadherin trafficking, from recycling endosomes to sites on the epithelial cell membrane where Armadillo is located.
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PMID:Drosophila exocyst components Sec5, Sec6, and Sec15 regulate DE-Cadherin trafficking from recycling endosomes to the plasma membrane. 1613 21

Cadherin-mediated adhesion plays an important role in maintaining cell-cell contacts and reducing tumor metastasis. However, neo-expression of E-cadherin in ovarian carcinoma does not prevent the release and spread of cells from the primary tumor. Because caveolin-1 is down-regulated concomitantly with E-cad expression, we investigated whether the stability of adherens junctions in ovarian carcinoma was affected by caveolin-1 expression. We used IGROV1 cells transfected with caveolin-1 (IGtC3), mock-transfected control cells (IGtM87), and SKOV3 cells that endogenously express caveolin-1. Simultaneous expression of caveolin-1 and E-cadherin favored membrane distribution of E-cadherin and its associated catenin (p120ctn), even when caveolin-1 was only focally associated with adherens junctions. Silencing of caveolin-1 induced intracellular E-cadherin redistribution in IGtC3 and SKOV3 cells. Treatment with the specific src kinase inhibitor PP1 increased E-cadherin expression in IGtM87 and SKOV3 cells and enhanced membrane localization of both E-cadherin and p120ctn. However, PP1 could not completely reverse the detrimental effects on cell-cell adhesion induced by Ca2+ depletion in IGtM87 cells. Together, our data suggest that caveolin-1 expression indirectly promotes cell-cell adhesion in ovarian carcinoma cells by a mechanism involving inhibition of src-related kinases. Thus, down-regulation or loss of caveolin-1 might contribute significantly to the spread of tumor cells from the primary tumor.
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PMID:Simultaneous expression of caveolin-1 and E-cadherin in ovarian carcinoma cells stabilizes adherens junctions through inhibition of src-related kinases. 1625 25

Cadherin-catenin complexes play a key role in embryonic development, and are associated with carcinogenesis and metastasis. We studied the expression of the major members of the family, including E-cadherin and beta-catenin in prostate cancer (PC), and correlated with Gleason grade and pathologic stage. Immunohistochemistry was performed on serial sections of paraffinized radical prostatectomy specimens to evaluate E-cadherin (n = 16) and beta-catenin (n = 17) expression using heat induced epitope retrieval. Benign appearing prostate epithelium was used as an internal control in each specimen. Two pathologists independently reviewed and scored the intensity and extent of immunostaining using a semiquantitative scale. The Mantel-Haenszel method, stratified by reviewer, was used to test for an association among Gleason score, pathologic stage, and the expression of E-cadherin or beta-catenin in PC. Gleason grade > or =7 cancers showed significantly lower expression of E-cadherin and beta-catenin compared to Gleason grade < 7 PC, P = 0.015 and 0.025, respectively. In addition, beta-catenin was down regulated in 4 of 5 (80%) specimens with identifiable high-grade prostatic intraepithelial neoplasia and had demonstrable nuclear staining in higher grade PC (P = 0.0001). However, E-cadherin and beta-catenin membranous or nuclear expressions were not significantly associated with final pathologic stage of the specimens (P values >0.05). Overall, the expression of E-cadherin and beta-catenin is significantly down regulated in PC compared to surrounding benign appearing prostate, which correlates with increasing Gleason grade. Furthermore, nuclear localization of beta-catenin in high grade PC may be a useful biomarker for aggressive PC.
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PMID:Aberrant expression of E-cadherin and beta-catenin in human prostate cancer. 1630 Nov 17

Approximately 310,000 new cases of oral and pharynx cancer account for a major cause of neoplasm related morbidity and mortality world-wide. Unfortunately, the survival rate has not improved significantly in the last decade. The vast majority of head and neck cancer is squamous cell carcinoma. The major adhesion-proteins involved in the development and maintenance of all solid tissue are the Cadherins. Cadherins are the transmembrane components of the adherent junction with interaction with plakoglobin and beta-catenin. Downregulation of Cadherins and catenins is frequently observed in many types of human cancer. Sulindac sulfone is one of the new therapeutic apoptotic agents that show promise in the treatment of cancer. In this study, we incubated sulindac sulfone with a head and neck cancer cell line and investigated the outcome of E-Cadherin. Immunohistochemical and Western blot analyses were then performed, with different concentrations of sulindac sulfone (100, 200, 400, 600, and 800 microMol) for 48 h. At 400 microMol of sulindac sulfone a decrease of 21% was observed; at 600 microMol, 44% decrease of beta-catenin concentration was seen, and incubation with 800 microMol resulted in 73% reduction of secreted beta-catenin. Incubation with sulindac sulfone seemed to stop proliferation; however, with respect to the controls, there was no increased reduction of the total protein. Sulindac sulfone resulted in an increase of E-Cadherin content in the head and neck squamous cell cancer cell line after 48 h of incubation; however, the reactivity was restricted to the adherent junctions. At increasing concentrations of sulindac sulfone, intercellular E-Cadherin immunostaining intensifyied. ELISA also depicted significant rising levels of E-Cadherin. Sulindac sulfone contributes to the inactivation of cGMP phospho-diesterase. Thus, the accumulation of cellular cGMP and protein kinase G is induced. The following degradation of the phosphorylated beta-catenin and the dissociation from the Cadherin-catenin complex releases E-Cadherin. This may also contribute to growth inhibition and co-ordinate with apoptosis induction. It is not really clear as to, which pathway results in the elevation of the E-Cadherin proteins. However, in epithelial cancer cells, the Cadherin-catenin complex serves as a target for the chemopreventive agent, sulindac sulfone.
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PMID:Chemopreventive alteration of the cell-cell adhesion in head and neck squamous cell cancer. 1682 Sep 2

Cadherin-catenin adhesion is pivotal for the development of multicellular organisms. Features such as a large repertoire of homotypically interacting cadherins, rapid assembly and disassembly, and a connection to a force-generating actin cytoskeleton make cadherin-mediated junctions ideal structures for the execution of complex changes in cell and tissue morphology during development. Recent findings highlight the role of cadherin-catenin proteins as critical regulators of major developmental pathways. We re-evaluate the significance of cadherin-catenin adhesion structures and propose that in addition to intercellular adhesion, they may be used as biosensors of the external cellular environment that help adjust the behavior of individual cells to ensure survival of the entire organism.
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PMID:Cadherin-catenin proteins in vertebrate development. 1685 5


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