EFFECT OF EPIDERMAL GROWTH-FACTOR ON CADHERIN-MEDIATED ADHESION IN A HUMAN ESOPHAGEAL CANCER CELL-LINE

Epidermal growth factor (EGF) mediates many pleiotrophic biological ef fects, one of which is alteration of cellular morphology. In the prese nt study, we examine the possibility that this alteration in cell morp hology is caused in part by the dysfunction of cadherin-mediated cell- cell adhesion using the human oesophageal cancer cell line TE-2R, whic h expresses E-cadherin and EGF receptor. In the presence of EGF, TE-2R changed its shape from round to fibroblastic and its colony formation from compact to sparse. Vanadate, a tyrosine phosphatase inhibitor, f urther potentiated the EGF response, whereas herbimycin A, a tyrosine kinase inhibitor, interfered with it. Moreover, EGF enabled the cells to invade in organotypic raft culture. These phenomena were accompanie d not by decreased expression of the E-cadherin molecule but by a chan ge in its localisation from the lateral adhesion site to the whole cel l surface. Both alpha- and beta-catenin, cadherin-binding proteins, we re also expressed at the same level throughout these morphological cha nges. Finally, we examined tyrosine phosphorylation of E-cadherin and alpha- and beta-catenin, and observed tyrosine phosphorylation of beta -catenin induced by EGF. These results suggest that EGF counteracts E- cadherin-mediated junctional assembly through phosphoryation of beta-c atenin and modulates tumour cell behaviour to a more aggressive phenot ype.