Emerging roles for p120-catenin in cell adhesion and cancer

Although originally identified as a Src substrate, p120-catenin (p120) is now known to regulate cell-cell adhesion through its interaction with the cytoplasmic tail of classical and type II cadherins. New evidence indicates that p120 regulates cadherin turnover at the cell surface, thereby controlling the amount of cadherin available for cell-cell adhesion. This function is necessary but not sufficient to promote strong adhesion, which is further controlled by signals acting on the amino-terminal p120 regulatory domain. p120 also modulates the activities of RhoA, Rac, and Cdc42, suggesting that along with other Src substrates, p120 regulates actin dynamics. Thus, p120 is a master regulator of cadherin abundance and activity, and likely participates in regulating the balance between adhesive and motile cellular phenotypes. This review summarizes recent progress in understanding mechanisms of p120 action, and discusses new implications with respect to roles for p120 in disease and cancer.