ECadherin

E-cadherin, or epithelial cadherin, is a calcium-dependent cell-cell adhesion molecule of the cadherin superfamily. It functions as a key component of adherens junctions in epithelial tissues, promoting homophilic adhesion between neighboring cells through its extracellular cadherin repeats. The extracellular region contains five cadherin repeats and requires Ca2+ to maintain a rigid, adhesive conformation.

The cytoplasmic tail binds catenins, including β-catenin and γ-catenin (plakoglobin) as well as p120-catenin, linking the complex to the actin cytoskeleton via α-catenin. This linkage supports cell polarity, tissue architecture, and mechanical integrity. Adhesion is dynamically regulated by endocytosis and proteolytic processing (e.g., ADAM10, matrix metalloproteinases) that shed the ectodomain and modulate junction turnover.

Genetics and expression: E-cadherin is encoded by the CDH1 gene on chromosome 16q22.1. It is expressed mainly in epithelial cells and serves as a marker of epithelial lineage.

Clinical significance: Loss or reduction of E-cadherin expression—often through CDH1 mutations, promoter hypermethylation, or transcriptional downregulation—removes adherens junctions and promotes epithelial-mesenchymal transition (EMT), a process linked to invasion and metastasis in cancer. Germline CDH1 mutations cause hereditary diffuse gastric cancer; somatic alterations are observed in diffuse-type gastric cancer, lobular breast cancer, and other carcinomas. E-cadherin loss is also associated with increased migratory behavior and poorer prognosis in various cancers.

Signaling and research note: By sequestering β-catenin at the membrane, E-cadherin can modulate Wnt signaling; disruption can release β-catenin to the nucleus. Because of its epithelial specificity, E-cadherin remains a widely used histological marker of epithelial cells and a focal point in EMT studies.