Synonyms |
CDH5, Cadherin-5, 7B4 antigen, Vascular endothelial cadherin, CD_antigen=CD144, Flags: Precursor |
Background |
Cadherins are a superfamily of transmembrane glycoproteins that contain cadherin repeats of approximately 100 residues in their extracellular domain. Cadherins mediate calcium-dependent cell-cell adhesion and play critical roles in normal tissue development (1). The classic cadherin subfamily includes N-, P-, R-, B- and E-cadherins, as well as about ten other members that are found in adherens junctions, a cellular structure near the apical surface of polarized epithelial cells. The cytoplasmic domain of classical cadherins interacts with beta-catenin, gamma-catenin (also called plakoglobin), and p120 catenin. beta-catenin and gamma-catenin associate with alpha-catenin, which links the cadherin-catenin complex to the actin cytoskeleton (1, 2). While beta- and gamma-catenin play structural roles in the junctional complex, p120 regulates cadherin adhesive activity and trafficking (1-4). E-cadherin is considered an active suppressor of invasion and growth of many epithelial cancers (1-3). Recent studies indicate that cancer cells have up-regulated N-cadherin in addition to loss of E-cadherin. This change in cadherin expression is called the "cadherin switch". N-cadherin cooperates with the FGF receptor, leading to overexpression of MMP-9 and cellular invasion (3). In endothelial cells, VE-cadherin signaling, expression, and localization correlate with vascular permeability and tumor angiogenesis (5, 6). Expression of P-cadherin, which is normally present in epithelial cells, is also altered in ovarian and other human cancers (7, 8). |