Beyond cell-cell adhesion: Plakoglobin and the regulation of tumorigenesis and metastasis

Plakoglobin (also known as gamma-catenin) is a member of the Armadillo family of proteins and a paralog of beta-catenin. Plakoglobin is a component of both the adherens junctions and desmosomes, and therefore plays a vital role in the regulation of cell-cell adhesion. Similar to beta-catenin, plakoglobin is capable of participating in cell signaling in addition to its role in cell-cell adhesion. In this context, beta-catenin has a well-documented oncogenic potential as a component of the Wnt signaling pathway. In contrast, while some studies have suggested a tumor promoting activity of plakoglobin in a cell/malignancy specific context, it generally acts as a tumor/metastasis suppressor. How plakoglobin acts as a growth/metastasis inhibitory protein has remained, until recently, unclear. Recent evidence suggests that plakoglobin may suppress tumorigenesis and metastasis by multiple mechanisms, including the suppression of oncogenic signaling, interactions with various proteins involved in tumorigenesis and metastasis, and the regulation of the expression of genes involved in these processes. This review is primarily focused on various mechanisms by which plakoglobin may inhibit tumorigenesis and metastasis.