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Yusuke Nakamura - One of the best experts on this subject based on the ideXlab platform.
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overexpressed p cadherin cdh3 promotes motility of pancreatic cancer cells by interacting with p120ctn and activating rho family gtpases
Cancer Research, 2005Co-Authors: Keisuke Taniuchi, Masayo Hosokawa, Toyomasa Katagiri, Toru Nakamura, Hidetoshi Eguchi, Hidewaki Nakagawa, Hiroaki Ohigashi, Osamu Ishikawa, Yusuke NakamuraAbstract:P-Cadherin/CDH3 belongs to the family of classic cadherins that are engaged in various cellular activities including motility, invasion, and signaling of tumor cells, in addition to cell adhesion. However, the biological roles of P-cadherin itself are not fully characterized. Based on information derived from a previous genome-wide cDNA microarray analysis of microdissected pancreatic ductal adenocarcinoma (PDAC), we focused on P-cadherin as one of the genes most strongly overexpressed in the great majority of PDACs. To investigate the consequences of overexpression of P-cadherin in terms of pancreatic carcinogenesis and tumor progression, we used a P-cadherin–deficient PDAC cell line, Panc-1, to construct a cell line (Panc1-CDH3) that stably overexpressed P-cadherin. Induction of P-cadherin in Panc1-CDH3 increased the motility of the cancer cells, but a blocking antibody against P-cadherin suppressed the motility in vitro. Overexpression of P-cadherin was strongly associated with cytoplasmic accumulation of one of the catenins, p120ctn, and cadherin switching in PDAC cells. Moreover, P-cadherin–dependent activation of cell motility was associated with activation of Rho GTPases, Rac1 and Cdc42, through accumulation of p120ctn in cytoplasm and cadherin switching. These findings suggest that overexpression of P-cadherin is likely to be related to the biological aggressiveness of PDACs; blocking of P-cadherin activity or its associated signaling could be a novel therapeutic approach for treatment of aggressive pancreatic cancers.
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Overexpressed P-Cadherin/CDH3 Promotes Motility of Pancreatic Cancer Cells by Interacting with p120ctn and Activating Rho-Family GTPases
Cancer Research, 2005Co-Authors: Keisuke Taniuchi, Masayo Hosokawa, Toyomasa Katagiri, Toru Nakamura, Hidetoshi Eguchi, Hidewaki Nakagawa, Hiroaki Ohigashi, Osamu Ishikawa, Yusuke NakamuraAbstract:P-Cadherin/CDH3 belongs to the family of classic cadherins that are engaged in various cellular activities including motility, invasion, and signaling of tumor cells, in addition to cell adhesion. However, the biological roles of P-cadherin itself are not fully characterized. Based on information derived from a previous genome-wide cDNA microarray analysis of microdissected pancreatic ductal adenocarcinoma (PDAC), we focused on P-cadherin as one of the genes most strongly overexpressed in the great majority of PDACs. To investigate the consequences of overexpression of P-cadherin in terms of pancreatic carcinogenesis and tumor progression, we used a P-cadherin–deficient PDAC cell line, Panc-1, to construct a cell line (Panc1-CDH3) that stably overexpressed P-cadherin. Induction of P-cadherin in Panc1-CDH3 increased the motility of the cancer cells, but a blocking antibody against P-cadherin suppressed the motility in vitro. Overexpression of P-cadherin was strongly associated with cytoplasmic accumulation of one of the catenins, p120ctn, and cadherin switching in PDAC cells. Moreover, P-cadherin–dependent activation of cell motility was associated with activation of Rho GTPases, Rac1 and Cdc42, through accumulation of p120ctn in cytoplasm and cadherin switching. These findings suggest that overexpression of P-cadherin is likely to be related to the biological aggressiveness of PDACs; blocking of P-cadherin activity or its associated signaling could be a novel therapeutic approach for treatment of aggressive pancreatic cancers.
Frans Van Roy - One of the best experts on this subject based on the ideXlab platform.
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Evolution of cadherins and associated catenins
The Cadherin Superfamily, 2016Co-Authors: Paco Hulpiau, Ismail Sahin Gul, Frans Van RoyAbstract:During more than 600 Ma of multicellular animal evolution, the cadherin superfamily has become strikingly diverse, both structurally and functionally. Cadherins are typically transmembrane proteins with an ectodomain comprising so-called cadherin repeats. Cadherins are involved in cell–cell recognition, intercellular adhesion, and associated signaling, and are major players in morphogenesis and tissue behavior. Members of the three major cadherin families (cadherins, protocadherins, and cadherin-related proteins) differ in many aspects from each other. E-cadherin is the best-studied family member. Its cytoplasmic domain binds armadillo catenins, which form linkages to the cytoskeleton and trigger complex signaling pathways. Alpha-catenins play complementary roles. Even basal animals such as placozoans and cnidarians express several distinct cadherins and catenins, and their study may identify paradigms for ancient though crucial biological processes. The complex domain compositions of the different superfamily members and their respective functionalities appear to be key features of the emergence of multicellular animal life. Moreover, the origin of vertebrates coincided with a large increase in the number of cadherins and armadillo proteins, including modern molecules such as contemporary “classical” cadherins, clustered protocadherins and plakophilins. Although much needs to be learned about the biology of cadherins, the steadily increasing knowledge on cadherins is fascinating and points to key roles in many biological processes and in several important pathologies. This chapter focuses on the evolutionary relationships between different cadherin family members. The aim is to contribute to a deeper insight into their versatile roles in metazoans, and to foster further research on this remarkable superfamily.
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Beyond E-cadherin: roles of other cadherin superfamily members in cancer
Nature Reviews Cancer, 2014Co-Authors: Frans Van RoyAbstract:The cadherin superfamily includes many proteins other than E-cadherin. These cadherins are very diverse in both structure and function, and their mutual interactions seem to influence cancer development and progression in complex and versatile ways. Loss of cadherin 1 (CDH1; also known as epithelial cadherin (E-cadherin)) is used for the diagnosis and prognosis of epithelial cancers. However, it should not be ignored that the superfamily of transmembrane cadherin proteins encompasses more than 100 members in humans, including other classical cadherins, numerous protocadherins and cadherin-related proteins. Elucidation of their roles in suppression versus initiation or progression of various tumour types is a young but fascinating field of molecular cancer research. These cadherins are very diverse in both structure and function, and their mutual interactions seem to influence biological responses in complex and versatile ways.
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Beyond E-cadherin: roles of other cadherin superfamily members in cancer
Nature reviews. Cancer, 2014Co-Authors: Frans Van RoyAbstract:Loss of cadherin 1 (CDH1; also known as epithelial cadherin (E-cadherin)) is used for the diagnosis and prognosis of epithelial cancers. However, it should not be ignored that the superfamily of transmembrane cadherin proteins encompasses more than 100 members in humans, including other classical cadherins, numerous protocadherins and cadherin-related proteins. Elucidation of their roles in suppression versus initiation or progression of various tumour types is a young but fascinating field of molecular cancer research. These cadherins are very diverse in both structure and function, and their mutual interactions seem to influence biological responses in complex and versatile ways.
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Involvement of Members of the Cadherin Superfamily in Cancer
Cold Spring Harbor perspectives in biology, 2009Co-Authors: Geert Berx, Frans Van RoyAbstract:We review the role of cadherins and cadherin-related proteins in human cancer. Cellular and animal models for human cancer are also dealt with whenever appropriate. E-cadherin is the prototype of the large cadherin superfamily and is renowned for its potent malignancy suppressing activity. Different mechanisms for inactivating E-cadherin/CDH1 have been identified in human cancers: inherited and somatic mutations, aberrant protein processing, increased promoter methylation, and induction of transcriptional repressors such as Snail and ZEB family members. The latter induce epithelial mesenchymal transition, which is also associated with induction of "mesenchymal" cadherins, a hallmark of tumor progression. VE-cadherin/CDH5 plays a role in tumor-associated angiogenesis. The atypical T-cadherin/CDH13 is often silenced in cancer cells but up-regulated in tumor vasculature. The review also covers the status of protocadherins and several other cadherin-related molecules in human cancer. Perspectives for emerging cadherin-related anticancer therapies are given.
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phylogenetic analysis of the cadherin superfamily allows identification of six major subfamilies besides several solitary members
Journal of Molecular Biology, 2000Co-Authors: Friedel Nollet, Patrick Kools, Frans Van RoyAbstract:Cadherins play an important role in specific cell-cell adhesion events. Their expression appears to be tightly regulated during development and each tissue or cell type shows a characteristic pattern of cadherin molecules. Inappropriate regulation of their expression levels or functionality has been observed in human malignancies, in many cases leading to aggravated cancer cell invasion and metastasis. The cadherins form a superfamily with at least six subfamilies, which can be distinguished on the basis of protein domain composition, genomic structure, and phylogenetic analysis of the protein sequences. These subfamilies comprise classical or type-I cadherins, atypical or type-II cadherins, desmocollins, desmogleins, protocadherins and Flamingo cadherins. In addition, several cadherins clearly occupy isolated positions in the cadherin superfamily (cadherin-13, -15, -16, -17, Dachsous, RET, FAT, MEGF1 and most invertebrate cadherins). We suggest a different evolutionary origin of the protocadherin and Flamingo cadherin genes versus the genes encoding desmogleins, desmocollins, classical cadherins, and atypical cadherins. The present phylogenetic analysis may accelerate the functional investigation of the whole cadherin superfamily by allowing focused research of prototype cadherins within each subfamily.
Luis A Diaz - One of the best experts on this subject based on the ideXlab platform.
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IgG Autoantibody Response Against Keratinocyte Cadherins in Endemic Pemphigus Foliaceus (Fogo Selvagem)
2016Co-Authors: Gustavo Flores, Valeria Aoki, Gunter Hans-filho, Donna A. Culton, Phillip Prisayanh, Bahjat F. Qaqish, Mike Maldonado, Kirk James, Ro A. Rivitti, Luis A DiazAbstract:It is well established that autoantibodies against desmoglein 3 and desmoglein 1 are relevant in the pathogenesis of pemphigus vulgaris and pemphigus foliaceus, including its endemic form, Fogo Selvagem (FS). Isolated reports have shown that in certain patients with these diseases, autoantibodies against other desmosomal cadherins and E-cadherin may also be present. The goal of this investigation was to determine if FS patients and normal individuals living in endemic areas possess autoantibodies against other desmosomal cadherins and E-cadherin. Testing a large number of FS and endemic control sera by ELISA we find a consistent and specific autoantibody response against desmoglein 1 and other keratinocyte cadherins in these individuals, which is quite different from US controls. Overall, the highest correlations among the autoantibody responses tested are in the endemic controls, followed by FS patients, and lowest in the US controls. These findings suggest that multiple, perhaps cross reactive, keratinocyte cadherins are recognized by FS patients and endemic controls
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IgG autoantibody response against keratinocyte cadherins in endemic pemphigus foliaceus (fogo selvagem).
The Journal of investigative dermatology, 2012Co-Authors: Gustavo Flores, Valeria Aoki, Gunter Hans-filho, Evandro A. Rivitti, Donna A. Culton, Phillip Prisayanh, Bahjat F. Qaqish, Kirk A. James, Mike Maldonado, Luis A DiazAbstract:It is well established that autoantibodies against desmoglein 3 and desmoglein 1 (Dsg1) are relevant in the pathogenesis of pemphigus vulgaris and pemphigus foliaceus, including its endemic form fogo selvagem (FS). Isolated reports have shown that in certain patients with these diseases, autoantibodies against other desmosomal cadherins and E-cadherin may also be present. The goal of this investigation was to determine whether FS patients and normal individuals living in endemic areas possess autoantibodies against other desmosomal cadherins and E-cadherin. By testing a large number of FS and endemic control sera by ELISA, we found a consistent and specific autoantibody response against Dsg1 and other keratinocyte cadherins in these individuals, which is quite different from healthy individuals from the United States (US controls). Overall, the highest correlations among the autoantibody responses tested were in the endemic controls, followed by FS patients, and lowest in the US controls. These findings suggest that multiple, perhaps cross-reactive, keratinocyte cadherins are recognized by FS patients and endemic controls.
Masatoshi Takeichi - One of the best experts on this subject based on the ideXlab platform.
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The cadherin superfamily in neuronal connections and interactions
Nature Reviews Neuroscience, 2007Co-Authors: Masatoshi TakeichiAbstract:The organization of neuronal circuits involves a number of processes that require cell–cell recognition and contacts. Cadherins are a family of cell–cell adhesion molecules comprising more than 100 members in vertebrates, which are grouped into subfamilies including classic cadherins, Flamingo/CELSRs and protocadherins, and are thought to have roles in various steps of neuronal cell interactions. N-cadherin and other vertebrate classic cadherins are essential not only for early morphogenesis of neural tissues but also for correct axon migration towards target areas, and for the extension of neuronal dendrites. Drosophila melanogaster N-cadherin ( D N-cadherin) has been shown to be crucial for the formation of axonal connections with target neurons in both the visual and olfactory systems, and also for confining dendritic arborizations to specific glomeruli in these systems. The activity of D N-cadherin during the axon targeting seems to be controlled by cytoplasmic proteins including leukocyte antigen-related-receptor protein tyrosine phosphatase (LAR). Flamingo, a seven-pass transmembrane cadherin, is required for the correct targeting of retinal axons in visual circuits in D. melanogaster . A vertebrate homologue of Flamingo, CELSR2, regulates dendritic arbor patterning in the cerebellum, and another homologue, CELSR3, is important for axon tract formation. Some protocadherins, which show a large diversification due to a unique gene organization, seem to be involved in synapse formation and neuronal survival. However, the biological roles of this subfamily remain largely unknown. In conclusion, members of the cadherin superfamily control axon–target recognition and connections, as well as other types of neuronal interactions in a subfamily-specific manner. The cadherin superfamily has roles in the development and organization of complex neuronal circuits. Takeichi explores the evidence from invertebrate and vertebrate studies for the involvement in these processes of different cadherin subfamilies, including classic cadherins, Flamingo/CELSRs and the protocadherins. Neural development and the organization of complex neuronal circuits involve a number of processes that require cell–cell interaction. During these processes, axons choose specific partners for synapse formation and dendrites elaborate arborizations by interacting with other dendrites. The cadherin superfamily is a group of cell surface receptors that is comprised of more than 100 members. The molecular structures and diversity within this family suggest that these molecules regulate the contacts or signalling between neurons in a variety of ways. In this review I discuss the roles of three subfamilies — classic cadherins, Flamingo/CELSRs and protocadherins — in the regulation of neuronal recognition and connectivity.
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cadherin 11 expressed in association with mesenchymal morphogenesis in the head somite and limb bud of early mouse embryos
Developmental Biology, 1995Co-Authors: Yoshishige Kimura, Hiroaki Matsunami, Takayoshi Inoue, Kenji Shimamura, Naoshige Uchida, Takehisa Ueno, Takahiro Miyazaki, Masatoshi TakeichiAbstract:Cadherin-11 (cad-11) is a novel member of the cadherin family of cell adhesion molecules, having recently been identified by means of the polymerase chain reaction. To study the function and expression of this molecule, we cloned mouse, cad-11 cDNA. Transfection of L cells with cDNA led them to acquire a typical cadherin-dependent cell-cell adhesiveness, and the L cells expressing cad-11 did not coaggregate with L cells expressing E-, P-, N-, or R-cadherin when they were mixed, indicating that this novel cadherin has a homophilic binding specificity, as found for other cadherins. To determine the developmental expression pattern of this molecule, we performed in situ hybridization analysis on early mouse embryos. Cad-11 first appeared in mesodermal layers only in the head and tail regions at the mid-to-late primitive streak stages. In the head, this appearance was followed by strong expression in mesenchymal tissues including branchial arches. In the trunk, the paraxial mesoderm initially did not express cad-11. However, as the somites formed, they expressed cad-11, and this expression was strictly correlated with their initial condensation and segregation from the presomitic mesoderm. The cad-11 expression in the somites was eventually restricted to sclerotome cells. As the limb buds developed, cad-11 appeared in the distal portion of the limb mesenchyme, and, at later stages, its expression was most evident at the peripheral mesenchyme. Cad-11 was thus expressed by restricted populations of mesenchymal cells in early embryos, although it was also expressed in parts of the neural tube, such as the optic vesicle and dorsal midline, and in part of the otic vesicle. As a step to investigate the role of cad-11 in mesenchymal cell adhesion, we dissociated the limb bud mesenchyme into single cells, pelleted them, and cultured them as aggregates. In these cultures, cad-11-positive cells clearly sorted out of the negative cell population, suggesting that cad-11 might be involved in selective association of mesenchymal cells. For comparison, we studied the expression of N-cadherin and found that the expressions of these two cadherins were differential, and complementary in some tissues. These results suggest that cad-11 is involved in specific associations of subsets of mesenchymal cells and also of some neural cells during early embryogenesis.
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Identification of a Drosophila homologue of alpha-catenin and its association with the armadillo protein.
The Journal of cell biology, 1993Co-Authors: Hiroki Oda, Shoichiro Tsukita, Tadashi Uemura, Kensuke Shiomi, Akira Nagafuchi, Masatoshi TakeichiAbstract:The cadherin cell adhesion system plays a central role in cell-cell adhesion in vertebrates, but its homologues are not identified in the invertebrate. alpha-Catenins are a group of proteins associated with cadherins, and this association is crucial for the cadherins' function. Here, we report the cloning of a Drosophila alpha-catenin gene by low stringent hybridization with a mouse alpha E-catenin probe. Isolated cDNAs encoded a 110-kD protein with 60% identity to mouse alpha E-catenin, and this protein was termed D alpha-catenin. The gene of this protein was located at the chromosome band 80B. Immunostaining analysis using a mAb to D alpha-catenin revealed that it was localized to cell-cell contact sites, expressed throughout development and present in a wide variety of tissues. When this protein was immunoprecipitated from detergent extracts of Drosophila embryos or cell lines, several proteins co-precipitated. These included the armadillo product which was known to be a Drosophila homologue of beta-catenin, another cadherin-associated protein in vertebrates, and a 150-kD glycoprotein. These results strongly suggest that Drosophila has a cell adhesion machinery homologous to the vertebrate cadherin-catenin system.
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cadherin cell adhesion receptors as a morphogenetic regulator
Science, 1991Co-Authors: Masatoshi TakeichiAbstract:Cadherins are a family of cell adhesion receptors that are crucial for the mutual association of vertebrate cells. Through their homophilic binding interactions, cadherins play a role in cell-sorting mechanisms, conferring adhesion specificities on cells. The regulated expression of cadherins also controls cell polarity and tissue morphology. Cadherins are thus considered to be important regulators of morphogenesis. Moreover, pathological examinations suggest that the down-regulation of cadherin expression is associated with the invasiveness of tumor cells.
Margaret J. Wheelock - One of the best experts on this subject based on the ideXlab platform.
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Differential displacement of classical cadherins by VE-cadherin.
Cell communication & adhesion, 2002Co-Authors: Meena Jaggi, Margaret J. Wheelock, Keith R. JohnsonAbstract:VE-cadherin is an endothelial cell-specific, type II classical cadherin that plays an important role in permeability, vasculogenesis, and vascular remodeling. Endothelial cells express equal levels of VE- and N-cadherin; VE-cadherin is present in junctions while N-cadherin is diffusely expressed over the surface of the cell. The present study was designed first to determine if the ability of VE-cadherin to displace N-cadherin from junctions was endothelial-cell specific, and second to determine if VE-cadherin could displace other classical cadherins from cell junctions. Our data suggest that VE-cadherin specifically influences the cellular localization of N-cadherin, independent of cell type, and does not effect the localization of other classical cadherins.
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Upregulation of P-cadherin expression in the lesional skin of pemphigus, Hailey-Hailey disease and Darier’s disease
Journal of Cutaneous Pathology, 2001Co-Authors: Megumi Hakuno, Margaret J. Wheelock, Masashi Akiyama, Hiroshi Shimizu, Takeji NishikawaAbstract:Background: Autoimmune blistering diseases, pemphigus vulgaris (PV) and pemphigus foliaceus (PF), are known to be caused by binding of autoantibodies to the desmosomal cadherins, desmoglein 3 and desmoglein 1, respectively. Recently, mutations in the genes coding Ca2+ pumps leads to inherited blistering diseases, Hailey-Hailey disease (HHD) and Darier’s disease (DD). Cadherins are a family of Ca2+-dependent cell adhesion molecules and P-cadherin is one of the major cadherins expressed in the epidermis. Although detailed mechanisms of acantholysis of these blistering diseases have not been fully clarified, abnormal expression of cadherins caused by altered Ca2+ concentration due to the binding of autoantibodies to cell surface or by mutations in Ca2+ pumps is suggested to be involved in mechanisms of acantholysis of these atuoimmune and inherited blistering diseases. The purpose of the present study was to determine whether altered P-cadherin expression is present in these diseases. Method: Distribution patterns of P-cadherin in skin specimens from patients with PV (n=2), PF (n=2), HHD (n=4) and DD (n=3), were examined with confocal laser scanning microscopy using two anti-P-cadherin antibodies, 6A9 and NCC-CAD-299. Results: In normal control skin, P-cadherin expression was restricted to the basal layer. In contrast, positive immunostaining of P-cadherin was observed not only in the basal cells, but also in the suprabasal cells in lesional skin of all the acantholytic diseases. Conclusions: The present results clearly demonstrated that upregulation of P-cadherin expression occurs in the acantholysis in all the four blistering diseases PV, PF, HHD and DD. Upregulation of P-cadherin may be involved in the pathomechanism of both the autoimmune blistering diseases and the inherited blistering diseases.
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upregulation of p cadherin expression in the lesional skin of pemphigus hailey hailey disease and darier s disease
Journal of Cutaneous Pathology, 2001Co-Authors: Megumi Hakuno, Margaret J. Wheelock, Masashi Akiyama, Hiroshi Shimizu, Takeji NishikawaAbstract:Background: Autoimmune blistering diseases, pemphigus vulgaris (PV) and pemphigus foliaceus (PF), are known to be caused by binding of autoantibodies to the desmosomal cadherins, desmoglein 3 and desmoglein 1, respectively. Recently, mutations in the genes coding Ca2+ pumps leads to inherited blistering diseases, Hailey-Hailey disease (HHD) and Darier’s disease (DD). Cadherins are a family of Ca2+-dependent cell adhesion molecules and P-cadherin is one of the major cadherins expressed in the epidermis. Although detailed mechanisms of acantholysis of these blistering diseases have not been fully clarified, abnormal expression of cadherins caused by altered Ca2+ concentration due to the binding of autoantibodies to cell surface or by mutations in Ca2+ pumps is suggested to be involved in mechanisms of acantholysis of these atuoimmune and inherited blistering diseases. The purpose of the present study was to determine whether altered P-cadherin expression is present in these diseases. Method: Distribution patterns of P-cadherin in skin specimens from patients with PV (n=2), PF (n=2), HHD (n=4) and DD (n=3), were examined with confocal laser scanning microscopy using two anti-P-cadherin antibodies, 6A9 and NCC-CAD-299. Results: In normal control skin, P-cadherin expression was restricted to the basal layer. In contrast, positive immunostaining of P-cadherin was observed not only in the basal cells, but also in the suprabasal cells in lesional skin of all the acantholytic diseases. Conclusions: The present results clearly demonstrated that upregulation of P-cadherin expression occurs in the acantholysis in all the four blistering diseases PV, PF, HHD and DD. Upregulation of P-cadherin may be involved in the pathomechanism of both the autoimmune blistering diseases and the inherited blistering diseases.
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Cadherin and catenin expression in normal human bronchial epithelium and non-small cell lung cancer.
Lung Cancer, 1999Co-Authors: W. Roy Smythe, Margaret J. Wheelock, Larry R Kaiser, John P. Williams, Steven M AlbeldaAbstract:Abstract Cadherins are transmembrane cell adhesion molecules (CAMS) that mediate cell–cell interactions and are important for maintenance of epithelial cell integrity. This function is dependent on an indirect interaction between the cytoplasmic domain of the cadherin molecule with three cytoplasmic proteins known as α-, β-, and γ-catenin (-cat). Growing evidence suggests that alterations in cadherin or catenin expression or function may be important to the development of an invasive or metastatic phenotype. Immunohistochemical techniques were used to study the expression of the two major epithelial cadherins, E-cadherin (E-cad) and P-cadherin (P-cad) as well as α- and γ-cat in normal bronchial epithelium and in a series of carefully TMN-staged pulmonary adenocarcinomas ( n =21) and squamous cell carcinomas ( n =7). The cadherin profile of normal pseudostratified bronchial epithelium was heterogeneous. Basilar cells strongly expressed P-cad, α- and γ-cat, while columnar cells moderately expressed E-cad, α- and γ-cat. In contrast to other epithelial tumors, E-cad on non-small cell lung carcinomas was actually upregulated, however, a decrease in P-cad expression was noted in 68%. At least one cadherin or catenin was downregulated, compared to normal bronchial epithelium, in 82% of tumors examined. With the exception of an association between loss of P-cad expression and poorly differentiated state, changes in cadherin and catenin expression levels were not significantly correlated to tumor stage, cell type, or nodal status. These findings illustrate that alteration of expression of cadherins and catenins are often found in non-small cell lung carcinoma when compared to the progenitor bronchial epithelium, and may play a role in the development of the malignant phenotype.
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e cadherin and p cadherin have partially redundant roles in human epidermal stratification
Cell and Tissue Research, 1997Co-Authors: Pamela J Jensen, Brett Telegan, Robert M Lavker, Margaret J. WheelockAbstract:Classical cadherins are Ca2+-dependent homotypic intercellular adhesion molecules that play major regulatory roles in tissue morphogenesis. Human epidermis, which expresses two classical cadherins (E- and P-cadherins), undergoes continual differentiation and morphogenesis, not just during embryonic development, but throughout life. The relative roles of E- and P-cadherin in epidermal morphogenesis have been studied in human epidermal keratinocytes in culture. In these cultures, tissue morphogenesis can be initiated simply by elevation of the extracellular Ca2+ concentration, which activates the cadherins, initiates desmosome organization, and then induces reorganization of the culture from a monolayer into a multilayered, more differentiated, epithelial-like structure. By examination of cultures after several days in high Ca2+, previous data have shown that concurrent inhibition of both E- and P-cadherins nearly abrogates the Ca2+-induced stratification response; however, it has not been possible to discern from these studies whether the two cadherins have unique or redundant regulatory properties. The present study has demonstrated, via electron-microscopic analysis of cultures at an early stage in stratification, that inhibition of either of the cadherins alone does not affect the initiation of stratification, i.e. the formation of up to 2–3 cell layers. Thus, E-cadherin and P-cadherin may have similar regulatory functions with respect to the initiation of stratification. However, if stratification is to continue further to produce a tissue-like structure of 5–7 cell layers, then E-cadherin is required and P-cadherin cannot act as a substitute, presumably because of the distinct localizations of E- and P-cadherins; E-cadherin is found in all cell layers of the stratified epithelium, whereas P-cadherin is lost after the basal keratinocytes become detached from the basement membrane and assume a suprabasal position. Therefore, basal cells, which have two cadherins, can utilize either cadherin to initiate stratification, whereas superficial cells, which have only E-cadherin, are dependent on this cadherin for further stratification.
