page 465, Ireton et al. report an unexpected mechanism by which cells can increase E-cadherin levels to boost their stickiness. Their findings stem from an unusual cell line that allows a direct analysis of the function of a cadherin modulator.
E-cadherin is the main cell–cell adhesion molecule in epithelial tissues. Down-regulation of E-cadherin occurs in many carcinoma types and correlates with the transition to metastasis. Recently, several tumor types have also been reported to have low levels of p120, a catenin thought to regulate the linkage of E-cadherin to the actin cytoskeleton. Now, Ireton et al. describe the first example of a carcinoma cell line—a colon cancer line, SW48—with mutations in p120 that cause low levels of the protein. This cell line reveals that p120 has a surprising effect on cadherin stability.
As expected, restoring expression of p120 rescued the adhesive phenotype of SW48 cells. Unexpectedly, the effect appears to be mediated by stabilization of the E-cadherin protein. Though it is still unclear how E-cadherin is stabilized, only forms of p120 that bound to the cadherin rescued the SW48 phenotype. One speculation is that p120 binding might displace cadherin destabilizers, such as presenilin or Hakai. Whatever the mechanism, the down-regulation of E-cadherin in some tumors could be a result of prior p120 loss. ▪