title: Induction of polarized cell-cell association and retardation of growth by activation of the E-cadherin-catenin adhesion system in a dispersed carcinoma line.
abstract: PC9 lung carcinoma cells cannot tightly associate with one another, and therefore grow singly, despite their expression of E-cadherin, because of their lack of alpha-catenin, a cadherin-associated protein. However, when the E-cadherin is activated by transfection with alpha-catenin cDNA, they form spherical aggregates, each consisting of an enclosed monolayer cell sheet. In the present work, we examined whether the alpha-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, and laminin. In untransfected PC9 cells, all these molecules were randomly distributed on their cell surface. In the transfected cells, however, each of them was redistributed into a characteristic polarized pattern without a change in the amount of expression. Electron microscopic study demonstrated that the alpha-catenin-transfected cell layers acquired apical-basal polarity typical of simple epithelia; they formed microvilli only on the outer surface of the aggregates, and a junctional 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 also found that, in untransfected PC9 cells, ZO-1 formed condensed clusters and colocalized with E-cadherin, but that other adhesion molecules rarely showed such colocalization with E-cadherin, suggesting that there is some specific interaction between ZO-1 and E-cadherin even in the absence of cell-cell contacts. In addition, we found that the activation of E-cadherin caused a retardation of PC9 cell growth. Thus, we concluded 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.
authors.affiliation: Department of Biophysics, Faculty of Science, Kyoto University, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Watabe
authors.forename: A
authors.initials: A
authors.lastname: Nagafuchi
authors.forename: S
authors.initials: S
authors.lastname: Tsukita
authors.forename: M
authors.initials: M
authors.lastname: Takeichi
mesh_terms: D015820:Cadherins / Q000032:analysis*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000032:analysis; D002455:Cell Division; D016764:Cell Polarity / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology*; D018076:DNA, Complementary; D004847:Epithelial Cells; D006801:Humans; D016023:Integrins / Q000032:analysis; D007365:Intercellular Junctions / Q000737:chemistry / Q000648:ultrastructure; D007797:Laminin; D008565:Membrane Proteins / Q000032:analysis; D010641:Phenotype; D010750:Phosphoproteins / Q000032:analysis; D014162:Transfection; D014407:Tumor Cells, Cultured; D062826:Zonula Occludens-1 Protein; D051178:alpha Catenin
chemical_list: C495273:CTNNA1 protein, human; D015820:Cadherins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D016023:Integrins; D007797:Laminin; D008565:Membrane Proteins; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D051178:alpha Catenin