Control of Carcinoma Cell Motility by E-Cadherin

摘要

Tumor invasion is a major obstacle to effective clinical management of breast cancer. To identify new targets for anti-invasive therapies, we have focused on the mechanisms by which the cell adhesion molecule E-cadherin suppresses tumor invasion. A related cadherin, N-cadherin, does not suppress cell movement, even though it is as effective as E-cadherin at mediating adhesion. We analyzed deletion mutants and exploited the difference between E- and N-cadherin to define regions of E-cadherin required for suppression of movement. We localized the key region that differs between E-cadherin and N- cadherin to a region consisting of the transmembrane segment and a small portion of the cytoplasmic domain, but demonstrated that E-cadherin does not regulate motility through sequestering pl 20, at physiological levels of expression. We also found that the catenin- binding domain is also required. Further, we identified two components that are tyrosine phosphorylated after E-cadherin contact, but determined they play no role in suppression of motility. We developed a new assay for analyzing the effect of cadherins on cell movement, which revealed that E-cadherin, but not N-cadherin, suppresses movement in intact monolayers of cells.