p120 catenin: an essential regulator of cadherin stability, adhesion-induced signaling, and cancer progression.

p120 catenin is the best studied member of a subfamily of proteins that associate with the cadherin juxtamembrane domain to suppress cadherin endocytosis. p120 also recruits the minus ends of microtubules to the cadherin complex, leading to junction maturation. In addition, p120 regulates the activity of Rho family GTPases through multiple interactions with Rho GEFs, GAPs, Rho GTPases, and their effectors. Nuclear signaling is affected by the interaction of p120 with Kaiso, a transcription factor regulating Wnt-responsive genes as well as transcriptionally repressing methylated promoters. Multiple alternatively spliced p120 isoforms and complex phosphorylation events affect these p120 functions. In cancer, reduced p120 expression correlates with reduced E-cadherin function and with tumor progression. In contrast, in tumor cells that have lost E-cadherin expression, p120 promotes cell invasion and anchorage-independent growth. Furthermore, p120 is required for Src-induced oncogenic transformation and provides a potential target for future therapeutic interventions.