Cadherin-catenin complex (CCC)

The cadherin-catenin complex is a fundamental protein assembly responsible for calcium-dependent cell-cell adhesion and the preservation of tissue polarity [PubMed: 25533351]. It consists of a transmembrane cadherin (e.g., E-cadherin) that forms homophilic bonds with cadherins on adjacent cells, while its cytoplasmic domain binds to p120-catenin and beta-catenin, which in turn recruits alpha-catenin to anchor the complex to the actin cytoskeleton [UniProt: P12830]. This complex functions as a vital signaling platform, modulating pathways such as Wnt/beta-catenin and Hippo to control cell proliferation, differentiation, and apoptosis [PubMed: 16025108]. In many epithelial cancers, the loss of E-cadherin or the disruption of the complex is a defining event of the epithelial-mesenchymal transition (EMT), facilitating tumor invasion and metastasis [NCBI: NBK556037]. Therapeutic interventions targeting this complex include the use of small peptides like ADH-1 (Exherin) to disrupt N-cadherin-mediated adhesion in solid tumors or monoclonal antibodies aimed at stabilizing adherens junctions [DrugBank: DB05313]. However, targeting these molecules presents significant challenges, as the complex is ubiquitous in healthy tissues, and its disruption can lead to severe side effects such as skin blistering or loss of intestinal barrier integrity [PubMed: 22102361].

Other names

Adherens junction complexCadherin complexE-cadherin-catenin complexCalcium-dependent cell-cell adhesion complex

Antagonism of cadherin-mediated adhesion through competitive binding to the extracellular domain [DrugBank: DB05313]