INDUCTION OF POLARIZED CELL-CELL ASSOCIATION AND RETARDATION OF GROWTH BY ACTIVATION OF THE E-CADHERIN CATENIN ADHESION SYSTEM IN A DISPERSED CARCINOMA LINE

PC9 lung carcinoma cells cannot tightly associate with one another, an d therefore grow singly, despite their expression of E-cadherin, becau se of their lack of alpha-catenin, a cadherin-associated protein. Howe ver, when the E-cadherin is activated by transfection with alpha-caten in cDNA, they form spherical aggregates, each consisting of an enclose d monolayer cell sheet. In the present work, we examined whether the a lpha-catenin-transfected cell layers expressed epithelial phenotypes, by determining the distribution of various cell adhesion molecules on their surfaces, including E-cadherin, ZO-1, desmoplakin, integrins, an d laminin. In untransfected PC9 cells, all these molecules were random ly distributed on their cell surface. In the transfected cells, howeve r, each of them was redistributed into a characteristic polarized patt ern without a change in the amount of expression. Electron microscopic study demonstrated that the alpha-catenin-transfected cell layers acq uired apical-basal polarity typical of simple epithelia; they formed m icrovilli only on the outer surface of the aggregates, and a junctiona l complex composed of tight junction, adherens junction, and desmosome arranged in this order. These results indicate that the activation of E-cadherin triggered the formation of the junctional complex and the polarized distribution of cell surface proteins and structures. We als o found that, in untransfected PC9 cells, ZO-1 formed condensed cluste rs and colocalized with E-cadherin, but that other adhesion molecules rarely showed such colocalization with E-cadherin, suggesting that the re is some specific interaction between ZO-1 and E-cadherin even in th e absence of cell-cell contacts. In addition, we found that the activa tion of E-cadherin caused a retardation of PC9 cell growth. Thus, we c oncluded that the E-cadherin-catenin adhesion system is essential not only for structural organization of epithelial cells but also for the control of their growth.