p120(ctn) acts as an inhibitory regulator of cadherin function in colon carcinoma cells

p120(ctn) binds to the cytoplasmic domain of cadherins but its role is poor ly understood. Cole 205 cells grow as dispersed cells despite their normal expression of E-cadherin and catenins. However, in these cells we can induc e typical E-cadherin-dependent aggregation by treatment with staurosporine or trypsin. These treatments concomitantly induce an electrophoretic mobili ty shift of p120(ctn) to a faster position. To investigate whether p120(ctn ) plays a role in this cadherin reactivation process, we transfected Cole 2 05 cells with a series of p120(ctn) deletion constructs. Notably, expressio n of NH2-terminally deleted p120(ctn) induced aggregation. Similar effects were observed when these constructs were introduced into HT-29 cells. When a mutant N-cadherin lacking the p120(ctn)-binding site was introduced into Cole 205 cells, this molecule also induced cell aggregation, indicating tha t cadherins can function normally if they do not bind to p120(ctn). These f indings suggest that in Cole 205 cells, a signaling mechanism exists to mod ify a biochemical state of p120(ctn) and the modified p120(ctn) blocks the cadherin system. The NH2 terminus-deleted p120(ctn) appears to compete with the endogenous p120(ctn) to abolish the adhesion-blocking action.