Bench to bedside and back again: molecular mechanisms of alpha-catenin function and roles in tumorigenesis.

The cadherin/catenin complex, comprised of E-cadherin, beta-catenin and alpha-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 beta-catenin in the Wnt signaling pathway has led to many studies of the role of beta-catenin in cancer. Alpha-catenin, in contrast, has received less attention. However, recent data demonstrate novel functions for alpha-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 alpha-catenin function, from the canonical role of alpha-catenin in cell-cell adhesion to non-canonical roles identified following conditional alpha-catenin deletion. This analysis identifies alpha-catenin as a prognostic factor in cancer progression.