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Epithelial Cells
Published in Bruce S. Bochner, Adhesion Molecules in Allergic Disease, 2020
The cadherins are a group of calcium-dependent cell-surface adhesion molecules that mediate cell–cell adhesion. They are made up of a single polypeptide chain and engage in homophilic adhesion of one cadherin molecule to another on an opposing cell membrane (60). Epithelial cadherin (E-cadherin, also called uvomorulin, Arc-1, liver cell adhesion molecule, L-CAM, and cell CAM 120/80) has been identified as a constituent of intermediate junctions in the bronchial epithelium. It localizes by immunofluorescence to the lateral cell membrane close to the luminal surface (45). Recent determination of the solution structure of E-cadherin revealed unexpected structural similarities to the immunoglobulin fold. The molecule has seven β-strands arranged in a “β-barrer topology, and two short α-helices, one of which provides the calcium-binding pocket. The putative adhesion interface is centered around the F-strand of the β-sheet and contains a conserved His-Ala-Val sequence (81). E-cadherin has been implicated in the suppression of tumor invasiveness, as its expression is decreased in the invasive phase of epithelial malignancies (82–84).
Basic Science and Molecular Oncology
Published in Manit Arya, Taimur T. Shah, Jas S. Kalsi, Herman S. Fernando, Iqbal S. Shergill, Asif Muneer, Hashim U. Ahmed, MCQs for the FRCS(Urol) and Postgraduate Urology Examinations, 2020
Paul Cleaveland, Vijay Sangar, Noel Clarke
Retinoblastoma (Rb) protein is a tumour suppressor protein, which is involved in preventing excessive cell growth by inhibiting the cell cycle until the point where the cell is ready to divide. At the point of cell division, it is phosphorylated rendering it inactive. p53 is a gene that codes for a protein that regulates the cell cycle and apoptosis. Defective p53 allows abnormal cells to proliferate and lead to cancer. Ki67 is a cellular marker for proliferation, which is associated with ribosomal RNA transcription. Inactivation of Ki67 leads to inhibition of ribosomal RNA synthesis. Increased expression is associated with aggressive pathological features. E-cadherin is a cell adhesion molecule that is involved in adherent junction formation, which allow cells to bind to one another. Decreased expression is associated with increased metastasis.
Hereditary Diffuse Gastric Cancer
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
The CDH1 gene is a 100 kb fragment organized in 16 exons, and encodes a 120 kDa calcium-dependent cellular adhesion protein called E-cadherin (or Cadherin-1), which has three domains (extracellular domain on the N-terminal, transmembrane domain in the center, and highly conserved cytoplasmic domain on the C-terminal) and demonstrates tumor suppressor functions. As a transmembrane glycoprotein predominantly expressed at the basolateral membrane of epithelial cells, E-cadherin mediates calcium-dependent cell−cell adhesion and invasion−suppression through interaction of its C-terminal with the actin cytoskeleton via undercoat proteins called catenins (α-, β-, and γ-), and contributes to the establishment and maintenance of polarized and differentiated epithelia during development. In addition, E-cadherin participates in signal transduction, differentiation, gene expression, cell motility, and inflammation [13].
Dual role of E-cadherin in cancer cells
Published in Tissue Barriers, 2022
Svetlana N. Rubtsova, Irina Y. Zhitnyak, Natalya A. Gloushankova
Loss of E-cadherin plays an important role in tumor progression. Down-regulation of E-cadherin expression detected in various carcinomas correlates with aggressive behavior of the tumors and is considered a prognostic factor associated with poor patient survival.39 Disruption of E-cadherin-based AJs between tumor cells facilitates their ability to migrate away from the tumor and invade adjacent tissues. Molecular mechanisms of E-cadherin down-regulation in tumors have been studied in great detail (Figure 2). Germline mutations inactivating the E-cadherin gene CDH1 and the subsequent loss of the E-cadherin protein were described in hereditary forms of diffuse gastric cancers and lobular breast cancers.40,41 Loss of heterozygosity on chromosome arm 16q in combination with a mutation of the other allele leading to CDH1 inactivation was revealed in many cases of hepatocellular carcinoma,42,43 prostate adenocarcinoma,44 and infiltrating lobular breast carcinoma.45,46 Aberrant methylation of the CDH1 gene promoter and the associated loss of E-cadherin expression was demonstrated in diffuse type gastric cancer and lobular breast carcinoma.47–49 In some cases, loss of E-cadherin in combination with inactivation of p53 or Pten has a causal role in tumor development as has been shown, for example, for invasive lobular breast carcinoma and diffuse type gastric cancer.50–52
Destiny of airway disease: interplay between epithelial barrier and the innate immune system
Published in Tissue Barriers, 2022
Barrier function is maintained by adherens junctions, homophilic E-Cadherin interactions, and intercellular contact formation.34 E-Cadherin binds to the actin cytoskeleton with Beta-Catenin stabilizing cell-cell. E-Cadherin downregulation is an essential component of the epithelial-mesenchymal transition (EMT), a process involved in cell migration, repair, and tissue remodeling. Many allergens contain proteases that cause epithelial damage. Proteases can also activate the ‘protease-activated receptor’ (PAR), which leads to proinflammatory gene transcription.35 PAR activation disrupts E-Cadherin-mediated cell-cell contact. Damaged epithelium induces the mesenchymal phenotype by showing increased sensitivity to noxious stimuli and inadequate repair response. Insufficient epithelial repair marker CD44 is supported by epidermal growth factor receptor (EGFR) and increased expression of TGF-Beta in damaged epithelium.29
Emerging therapeutic targets for gastric cancer from a host-Helicobacter pylori interaction perspective
Published in Expert Opinion on Therapeutic Targets, 2021
Esmat Abdi, Saeid Latifi-Navid, Fatemeh Abedi Sarvestani, Mohammad Hassan Esmailnejad
HtrA has shown proteolytic activity for HP. It also directly affects the infection process. Extracellular HtrA is responsible for the cleavage of the cell adhesion protein and tumor suppressor E-cadherin in gastric epithelial cells. The fibronectin as an extracellular matrix (ECM) macromolecule recognized as a substrate for HP HtrA [56,57]. This indicates the greater importance of HtrA activity in HP-induced GC. E-cadherin is a crucial molecule in the epithelial architecture and is involved in functional intercellular adhesions. A substrate-derived inhibitor peptide and small molecule compounds can stop the HtrA activity to effectively prevent the E-cadherin cleavage in vitro and bacterial transmigration; suggesting that the E-cadherin cleavage can be pharmacologically stopped by the HtrA secreted by HP, and can act as a potential structure for future therapies [56,58,59].