Cadherin superfamily (CDH)

Cadherins are a superfamily of calcium-dependent transmembrane glycoproteins that serve as the primary mediators of homophilic cell-cell adhesion, playing a fundamental role in tissue morphogenesis and the maintenance of structural integrity. These proteins are characterized by an extracellular domain containing multiple cadherin repeats that bind calcium ions to facilitate adhesion, and a cytoplasmic tail that interacts with catenins to link the adhesion complex to the actin cytoskeleton. Beyond their structural roles, cadherins function as dynamic signaling receptors that modulate pathways such as Wnt/beta-catenin, TGF-beta, and EGFR, thereby regulating cell proliferation, survival, and differentiation. In pathological contexts, particularly oncology, the "cadherin switch"—marked by the downregulation of E-cadherin and upregulation of N-cadherin—is a critical driver of the epithelial-mesenchymal transition (EMT), which promotes tumor invasion and metastasis. Therapeutic targeting of cadherins has focused on disrupting these interactions using small molecules like ADH-1 (Exherin) or monoclonal antibodies, though the widespread expression of cadherins in normal tissues necessitates careful consideration of off-target toxicity and systemic safety.

Other names

Calcium-dependent adhesion moleculeCDHsUvomorulinL-CAMCell-cell adhesion molecule

Antagonism of homophilic extracellular domain interactions to disrupt cell-cell adhesion and downstream signaling pathways, such as the Wnt/beta-catenin and TGF-beta cascades, often leading to tumor vascular disruption or inhibition of EMT-mediated metastasis.