α-catenin A tumor suppressor beyond adherens junctions

Downregulation or loss of alpha-catenin occurs in multiple human cancer types. The traditional view of alpha-catenin is that it is one of the core components of the E-cadherin-catenin complex and is required for maintaining the integrity of the intercellular adherens junction, a cell junction whose cytoplasmic face is linked to the actin cytoskeleton. Therefore, loss of alpha-catenin can result in loss of cell-cell adhesion, a common characteristic of cancer cells. There is an emerging recognition; however, that alpha-catenin also regulates multiple signaling pathways independent of adherens junctions. For instance, alpha-catenin functions as a tumor suppressor in E-cadherin-negative basal like breast cancer cells by inhibiting NF-kappa B signaling. In this perspective, we discuss the role and mechanisms of alpha-catenin in regulating several signaling pathways in cancer.