Bench to bedside and back again: Molecular mechanisms of α-catenin function and roles in tumorigenesis

The cadherin/catenin complex, comprised of E-cadherin, β-catenin and α-catenin, is essential for initiating cell–cell adhesion, establishing cellular polarity and maintaining tissue organization. Disruption or loss of the cadherin/catenin complex is common in cancer. As the primary cell–cell adhesion protein in epithelial cells, E-cadherin has long been studied in cancer progression. Similarly, additional roles for β-catenin in the Wnt signaling pathway has led to many studies of the role of β-catenin in cancer. Alpha-catenin, in contrast, has received less attention. However, recent data demonstrate novel functions for α-catenin in regulating the actin cytoskeleton and cell–cell adhesion, which when perturbed could contribute to cancer progression. In this review, we use cancer data to evaluate molecular models of α-catenin function, from the canonical role of α-catenin in cell–cell adhesion to non-canonical roles identified following conditional α-catenin deletion. This analysis identifies α-catenin as a prognostic factor in cancer progression.