Statistics from Altmetric.com
Epithelial-cadherin (E-cadherin; encoded by CDH1) is a member of the classical cadherins (the others being neural cadherin (N-cadherin) and vascular endothelial cadherin (VE-cadherin)). These single-pass transmembrane glycoproteins are expressed by a variety of tissues and are involved in Ca2+-dependent cell–cell adhesion. Initially described as liver cell adhesion molecule in chickens1 and uvomorulin in mice,2 the name E-cadherin was first used by Takeichi and colleagues in the early 1980s.3 ,4 Since then its role in normal epithelial cell architecture and tissue formation, as well as a tumour suppressor gene in cancer development and progression, has been extensively studied. Cell–cell adhesions are vital to maintain the integrity of cells and cohesion of tissues, and the control of these junctions therefore plays an important part in tumourigenesis. E-cadherin mediates cell–cell contact at the basolateral membrane in adherens junctions and its expression is the hallmark of epithelial cell layers.5 This short review focuses on the structure and function of E-cadherin at the cell junction, including the cadherin–catenin complex and its involvement in epithelial-to-mesenchymal transition (EMT). Finally, the role of E-cadherin in cancer and the therapeutic implications are discussed.
Structure and function
The CDH1 gene is located on chromosome 16q22.1, spanning a region of approximately 100 kb.6 CDH1 comprises 16 exons and 15 introns and is highly conserved between species.6 The resulting E-cadherin protein is a 120 kDa glycoprotein consisting of an extracellular domain of five tandem repeated domains, a cytoplasmic domain and a single transmembrane domain.7 ,8 The extracellular domain has binding sites for Ca2+ ions and extends from the cell surface to bind to cadherins on adjacent cells by lateral dimerisation.9 This allows a cadherin–cadherin interface and thus cell–cell adhesion. The cytoplasmic domain consists of the juxtamembrane domain (JMD) and the catenin-binding domain (CBD), each …