Faculty Opinions recommendation of Calcium-dependent homoassociation of E-cadherin by NMR spectroscopy: changes in mobility, conformation and mapping of contact regions.

2003 ◽  
Author(s):  
Deborah Leckband
Keyword(s):  
Nmr Spectroscopy ◽  
Calcium Dependent ◽  
E Cadherin

Calcium-dependent Homoassociation of E-cadherin by NMR Spectroscopy: Changes in Mobility, Conformation and Mapping of Contact Regions

2002 ◽  
Vol 324 (4) ◽  
pp. 823-839 ◽  
Author(s):  
Daniel Häussinger ◽  
Thomas Ahrens ◽  
Hans-Jürgen Sass ◽  
Olivier Pertz ◽  
Jürgen Engel ◽  
...  
Keyword(s):  
Nmr Spectroscopy ◽  
Calcium Dependent ◽  
E Cadherin

Mislocalization of Adherens Junction- Associated Proteins in a Patient with Darier Disease

2018 ◽  
Vol 2 (3) ◽  
pp. 184-201
Author(s):  
George D Glinos ◽  
Irena Pastar ◽  
Marjana Tomic-Canic ◽  
Rivka C Stone
Keyword(s):  
Adherens Junction ◽  
Cellular Adhesion ◽  
Calcium Flux ◽  
Keratinocyte Differentiation ◽  
Calcium Dependent ◽  
Endoplasmic Reticulum Calcium ◽  
Darier Disease ◽  
Associated Proteins ◽  
Attachment Proteins ◽  
E Cadherin

Darier disease (DD) is an autosomal dominant keratinizing genodermatosis that manifests clinically with red-brown pruritic papules in a seborrheic distribution often in association with palmoplantar pits and dystrophic nail changes. It is caused by mutation in ATP2A2 which encodes a sarco/endoplasmic reticulum calcium ATPase isoform 2 (SERCA2) pump that regulates calcium flux. Consequent alteration of intracellular calcium homeostasis is thought to impair trafficking of cellular adhesion proteins and to lead to aberrant keratinocyte differentiation, contributing to the characteristic histopathologic features of acantholysis and dyskeratosis in DD, though the precise mechanisms are incompletely understood. Previous studies have identified defective localization of desmosomal attachment proteins in skin biopsies and cultured keratinocytes from DD patients, but reports of effects on adherens junction proteins (including calcium-dependent E-cadherin) are conflicting. Here we describe a case of DD presenting with characteristic clinical and histologic features in which we performed immunofluorescence staining of four adherens junction-associated proteins (E-cadherin, α-catenin, β-catenin, and vinculin). In lesional (acantholytic) DD skin, we identified loss of distinctive bright membranous staining that was present at the periphery of keratinocytes throughout the epidermis in the healthy skin of a matched donor. Perilesional (non-acantholytic) portions of DD skin partially recapitulated the normal phenotype. Our findings support a role for SERCA2 dysfunction in impaired assembly of adherens junctions, which together with defective desmosomes contribute to acantholysis in DD.

scholarly journals E-Cadherin: An Important Functional Molecule at Respiratory Barrier Between Defence and Dysfunction

2021 ◽  
Vol 12 ◽  
Author(s):  
Hasan Yuksel ◽  
Merve Ocalan ◽  
Ozge Yilmaz
Keyword(s):  
Respiratory Diseases ◽  
Environmental Pollutants ◽  
Airway Epithelial ◽  
Internal Environment ◽  
Physical Barrier ◽  
Human Respiratory Tract ◽  
Calcium Dependent ◽  
Human Airways ◽  
E Cadherin

While breathing, many microorganisms, harmful environmental particles, allergens, and environmental pollutants enter the human airways. The human respiratory tract is lined with epithelial cells that act as a functional barrier to these harmful factors and provide homeostasis between external and internal environment. Intercellular epithelial junctional proteins play a role in the formation of the barrier. E-cadherin is a calcium-dependent adhesion molecule and one of the most important molecules involved in intercellular epithelial barier formation. E-cadherin is not only physical barrier element but also regulates cell proliferation, differentiation and the immune response to environmental noxious agents through various transcription factors. In this study, we aimed to review the role of E-cadherin in the formation of airway epithelial barier, its status as a result of exposure to various environmental triggers, and respiratory diseases associated with its dysfunction. Moreover, the situations in which its abnormal activation can be noxious would be discussed.

scholarly journals Structure-Based Virtual Screening Allows the Identification of Efficient Modulators of E-Cadherin-Mediated Cell–Cell Adhesion

2019 ◽  
Vol 20 (14) ◽  
pp. 3404 ◽  
Author(s):  
Andrea Dalle Vedove ◽  
Federico Falchi ◽  
Stefano Donini ◽  
Aurelie Dobric ◽  
Sebastien Germain ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Virtual Screening ◽  
Adherens Junction ◽  
Large Family ◽  
Calcium Dependent ◽  
Molecule Inhibitor ◽  
Dependent Cell ◽  
Cell Adhesion Proteins ◽  
E Cadherin ◽  
Cell Cell

Cadherins are a large family of transmembrane calcium-dependent cell adhesion proteins that orchestrate adherens junction formation and are crucially involved in tissue morphogenesis. Due to their important role in cancer development and metastasis, cadherins can be considered attractive targets for drug discovery. A recent crystal structure of the complex of a cadherin extracellular portion and a small molecule inhibitor allowed the identification of a druggable interface, thus providing a viable strategy for the design of cadherin dimerization modulators. Here, we report on a structure-based virtual screening approach that led to the identification of efficient and selective modulators of E-cadherin-mediated cell–cell adhesion. Of all the putative inhibitors that were identified and experimentally tested by cell adhesion assays using human pancreatic tumor BxPC-3 cells expressing both E-cadherin and P-cadherin, two compounds turned out to be effective in inhibiting stable cell–cell adhesion at micromolar concentrations. Moreover, at the same concentrations, one of them also showed anti-invasive properties in cell invasion assays. These results will allow further development of novel and selective cadherin-mediated cell–cell adhesion modulators for the treatment of a variety of cadherin-expressing solid tumors and for improving the efficiency of drug delivery across biological barriers.

scholarly journals N-Cadherin Promotes Motility in Human Breast Cancer Cells Regardless of Their E-Cadherin Expression

1999 ◽  
Vol 147 (3) ◽  
pp. 631-644 ◽  
Author(s):  
Marvin T. Nieman ◽  
Ryan S. Prudoff ◽  
Keith R. Johnson ◽  
Margaret J. Wheelock
Keyword(s):  
Breast Cancer ◽  
Epithelial Cell ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Direct Role ◽  
Fgf Receptor ◽  
Calcium Dependent ◽  
Transmembrane Glycoprotein ◽  
Invasive Capacity ◽  
E Cadherin

E-cadherin is a transmembrane glycoprotein that mediates calcium-dependent, homotypic cell–cell adhesion and plays a role in maintaining the normal phenotype of epithelial cells. Decreased expression of E-cadherin has been correlated with increased invasiveness of breast cancer. In other systems, inappropriate expression of a nonepithelial cadherin, such as N-cadherin, by an epithelial cell has been shown to downregulate E-cadherin expression and to contribute to a scattered phenotype. In this study, we explored the possibility that expression of nonepithelial cadherins may be correlated with increased motility and invasion in breast cancer cells. We show that N-cadherin promotes motility and invasion; that decreased expression of E-cadherin does not necessarily correlate with motility or invasion; that N-cadherin expression correlates both with invasion and motility, and likely plays a direct role in promoting motility; that forced expression of E-cadherin in invasive, N-cadherin–positive cells does not reduce their motility or invasive capacity; that forced expression of N-cadherin in noninvasive, E-cadherin–positive cells produces an invasive cell, even though these cells continue to express high levels of E-cadherin; that N-cadherin–dependent motility may be mediated by FGF receptor signaling; and that cadherin-11 promotes epithelial cell motility in a manner similar to N-cadherin.

scholarly journals Plakoglobin, or an 83-kD homologue distinct from beta-catenin, interacts with E-cadherin and N-cadherin.

1992 ◽  
Vol 118 (3) ◽  
pp. 671-679 ◽  
Author(s):  
K A Knudsen ◽  
M J Wheelock
Keyword(s):  
Cell Adhesion ◽  
Cell Surface ◽  
Molecular Mass ◽  
Beta Catenin ◽  
Calcium Dependent ◽  
Intracellular Proteins ◽  
Dependent Cell ◽  
Cell Surface Glycoproteins ◽  
E Cadherin ◽  
Cell Cell

E- and N-cadherin are members of a family of calcium-dependent, cell surface glycoproteins involved in cell-cell adhesion. Extracellularly, the transmembrane cadherins self-associate, while, intracellularly, they interact with the actin-based cytoskeleton. Several intracellular proteins, collectively termed catenins, have been noted to co-immunoprecipitate with E- and N-cadherin and are thought to be involved in linking the cadherins to the cytoskeleton. Two catenins have been identified recently: a 102-kD vinculin-like protein (alpha-catenin) and a 92-kD Drosophila armadillo/plakoglobin-like protein (beta-catenin). Here, we show that plakoglobin, or an 83-kD plakoglobin-like protein, co-immunoprecipitates and colocalizes with both E- and N-cadherin. The 83-kD protein is immunologically distinct from the 92-kD beta-catenin and, because of its molecular mass, likely represents the cadherin-associated protein called gamma-catenin. Thus, two different members of a plakoglobin family associate with N- and E-cadherin and, together with the 102-kD alpha-catenin, appear to participate in linking the cadherins to the actin-based cytoskeleton.

scholarly journals Expression of Wnt-1 in PC12 cells results in modulation of plakoglobin and E-cadherin and increased cellular adhesion.

1993 ◽  
Vol 123 (6) ◽  
pp. 1857-1865 ◽  
Author(s):  
R S Bradley ◽  
P Cowin ◽  
A M Brown
Keyword(s):  
Cell Adhesion ◽  
Pc12 Cells ◽  
Morphological Changes ◽  
Fetal Brain ◽  
Cell Types ◽  
Cellular Adhesion ◽  
Signaling Mechanism ◽  
Calcium Dependent ◽  
Junction Protein ◽  
E Cadherin

The Wnt-1 gene plays an essential role in fetal brain development and encodes a secreted protein whose signaling mechanism is presently unknown. In this report we have investigated intracellular mechanisms by which the Wnt-1 gene induces morphological changes in PC12 pheochromocytoma cells. PC12 cells expressing Wnt-1 show increased steady-state levels of the adhesive junction protein plakoglobin, and an altered distribution of this protein within the cell. This effect appears similar to a modulation of the plakoglobin homolog, Armadillo, that occurs in Drosophila embryos in response to the Wnt-1 homolog, wingless (Riggleman, B., P. Schedl, and E. Wieschaus. 1990. Cell. 63:549-560). In addition, PC12/Wnt-1 cells show elevated expression of E-cadherin and increased calcium-dependent cell-cell adhesion. These results imply evolutionary conservation of cellular responses to Wnt-1/wingless and indicate that in certain cell types Wnt-1 may act to modulate cell adhesion mechanisms.

scholarly journals Aberrant expression of E-cadherin in infiltrating ductal and lobular breast carcinomas and its correlation with clinicopathological parameters – A hospital-based study

2021 ◽  
Vol 7 (3) ◽  
pp. 99-109
Author(s):  
Shruthi T ◽  
◽  
Dr. Ramesh Chavan ◽  
Dr. Naresh Jaikumar Kulkarni ◽  
◽  
...  
Keyword(s):  
Lobular Carcinoma ◽  
Surgical Margin ◽  
Clinicopathological Parameters ◽  
Breast Carcinomas ◽  
Malignant Tumours ◽  
Aberrant Expression ◽  
Retrieval Method ◽  
Calcium Dependent ◽  
Ductal Carcinomas ◽  
E Cadherin

Introduction: Breast carcinoma is one of the commonest malignant tumours in women, leading topremature deaths and morbidity. E-cadherin is a 120kDa calcium-dependent transmembraneglycoprotein encoded by the CDH1 gene located on chromosome 16q21 and is expressed in mostepithelial cells. Loss of E Cadherin expression implies cell discohesion and favours metastasis.Materials and Methods: A total of 30 cases of breast carcinomas were studied, over two years.Histological grade and type were assessed by staining the paraffin-embedded sections with H & E.Using IHC technique, E-cadherin antigen was retrieved by Heat-Induced Epitome Retrieval method,and immunostaining was scored semiquantitatively. Cases were grouped as ‘preserved,’ whenpositivity was strong membranous, and occurred in more than 75% of the neoplastic epithelial cellsand ‘aberrant’ in all the remaining cases. Results: E-cadherin was found to be preserved in 46.7%of all the breast carcinomas and aberrant in 51.7% of invasive ductal carcinomas (IDC) alone, while100% of invasive lobular carcinomas showed aberrant expression. No significant correlation wasfound with E-cadherin grading and histological type of carcinoma, histopathological grade orinvolvement of deep surgical margin. Conclusion: Differentiation between invasive ductal andinvasive lobular carcinoma based on the loss of E-cadherin has to be done cautiously given itsaberrant expression in ductal carcinomas as well.

scholarly journals Downregulation of Thrombomodulin, a Novel Target of Snail, Induces Tumorigenesis through Epithelial-Mesenchymal Transition

2010 ◽  
Vol 30 (20) ◽  
pp. 4767-4785 ◽  
Author(s):  
Yuan-Chung Kao ◽  
Li-Wha Wu ◽  
Chung-Sheng Shi ◽  
Che-Hsien Chu ◽  
Chia-Wei Huang ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Cell Model ◽  
Cell Junctions ◽  
A431 Cells ◽  
Mesenchymal Transition ◽  
Calcium Dependent ◽  
Downstream Target ◽  
Novel Target ◽  
Immunocompromised Mice ◽  
E Cadherin

ABSTRACT The expression of thrombomodulin (TM), a calcium-dependent adhesion molecule, is frequently downregulated in various cancer types. However, the mechanism responsible for the low expression level of TM in tumorigenesis is unknown. Here, an inverse expression of TM and Snail was detected in different cancer cell lines. We further confirmed this inverse relation using the epithelial-mesenchymal transition cell model in HaCaT and A431 cells. We demonstrated that Snail suppressed TM expression by binding to E-box (CACCTG) in TM promoter. Moreover, TM knockdown by short hairpin RNA disrupted E-cadherin-mediated cell junctions and contributed to tumorigenesis. In the calcium switch assay, E-cadherin lost the ability to associate with β-catenin and accumulated in cytoplasm in TM knockdown cells. Meanwhile, wound healing and invasive assays showed that TM knockdown promoted cell motility. A subcutaneous injection of TM knockdown transfectants into immunocompromised mice induced squamous cell carcinoma-like tumors. Besides, forced expression of murine TM in TM knockdown cells made the cells reassume epithelium-like morphology and increased calcium-dependent association of E-cadherin and β-catenin. In conclusion, TM, a novel downstream target of Snail in epithelial-mesenchymal transition, is required for maintaining epithelial morphology and functions as a tumor suppressor.

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