Activation Of Epidermal Growth Factor Receptor (EGFR) And Its Downstream Signaling Transduction By Formation Of E-Cadherin Mediated Cell-Cell Adhesion In Ovarian Cancer Cells

BackgroundCadherins are a large kind of important adhesive molecules which mediate homophilic cell-cell interactions to regulate cellular differentiation and morphological development, including epidermal cadherin (E-cadherin), hepatic cadherin (H-cadherin), placental cadherin (P-cadherin) and neural cadherin (N-cadherin). E-cadherin molecules can establish calcium-dependent homophilic interactions through their extracellular domain, and these bindings are stabilized by the association of the intracellular domain with a, β, and γ-catenins, which are linked to F-actin to form functional adherens junctions, and are essential for E-cadherin to function as a regulator of cellular biological behaviors.E-cadherin is an important member of cadherin family. Its gene, CDH1, is located in region 22.1 on the long arm of chromosome 16, including 16 exons and 15 introns, encoding a 120-kDa transmembrane calcium-dependent glycoprotein, with a shorter soluble proteolytic product of 80 kDa. E-cadherin plays a major role in epithelial cell adhesion and is composed of three parts-the extracellular, transmembrane and intracellular domain. Its extracellular part consists of 5 repeated homologous structural domains and each has specific sites for calcium binding. The structural domains turn from sphericity to stick-like once binded by calcium and in turn mediate cell-cell adhesion. The binding of cadherins to a group of cytoplasmic proteins, the catenins, forms the zonula adherens, and these structures participate in cell junction formation and tissue stabilization.