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. 2014;13(15):2334-9.
doi: 10.4161/cc.29765.

α-catenin. A tumor suppressor beyond adherens junctions

Yutong Sun  1 , Jinsong Zhang, Li Ma
Affiliations

α-catenin. A tumor suppressor beyond adherens junctions

Yutong Sun et al. Cell Cycle. 2014.

Abstract

Downregulation or loss of α-catenin occurs in multiple human cancer types. The traditional view of α-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 α-catenin can result in loss of cell-cell adhesion, a common characteristic of cancer cells. There is an emerging recognition; however, that α-catenin also regulates multiple signaling pathways independent of adherens junctions. For instance, α-catenin functions as a tumor suppressor in E-cadherin-negative basal like breast cancer cells by inhibiting NF-κB signaling. In this perspective, we discuss the role and mechanisms of α-catenin in regulating several signaling pathways in cancer.

Keywords: Hedgehog; NF-kB; YAP; cancer; tumor suppressor; α-catenin; β-catenin.

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Figures

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Figure 1. α-catenin signaling in cancer. In addition to maintaining the integrity of the cadherin-catenin complex and linking adherens junctions to the actin cytoskeleton, α-catenin can: (1) inhibit the Wnt/β-catenin pathway by preventing β-catenin nuclear translocation or formation of the β-catenin-TCF-DNA complex, by promoting β-catenin degradation, or by recruiting APC to the β-catenin-TCF complex; (2) regulate the Hippo-YAP pathway by blocking YAP dephosphorylation and nuclear localization; and (3) suppress the NF-κB pathway by inhibiting IκB ubiquitination and its association with the proteasome, in a tissue type-specific manner. The Hedgehog pathway is not shown, as it is unknown how this pathway is regulated by α-catenin.
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