Abstract
Previous studies found that overexpression of the epidermal growth factor receptor (EGF-R) and reduced expression of E-cadherin and α-caenin were associated with lymph node metastasis of esophageal cancer. In the present study, we examined whether EGF was in part responsible for the dysfunction of cadherin-mediated cell-cell adhesion in the human esophageal cancer cell line TE-2R, which expresses E-cadherin and EGF-R. In the presence of EGF, TE-2R changed its colony formation from compact to sparse. In the cell dissociation assay, EGF strongly facilitated the dissociation of TE-2R cells in a dose-dependent manner. Moreover, EGF enabled the cells to invade an organotypic raft culture. These phenomena were accompanied not by decreased expression of the E-cadherin molecule but by a change in its location from the lateral adhesion site to the whole cell surface. Finally, we observed tyrosine phosphorylation of β-catenin induced by EGF. These results suggest that EGF might counteract Ecadherin mediated cell-cell adhesion through phosphorylation of β-catenin and modulate tumor cells to a more aggressive phenotype for lymph node metastasis of esophageal cancer.
