EXPRESSION OF N-CADHERIN BY HUMAN SQUAMOUS CARCINOMA-CELLS INDUCES A SCATTERED FIBROBLASTIC PHENOTYPE WITH DISRUPTED CELL-CELL ADHESION

E-cadherin is a transmembrane glycoprotein that mediates calcium-depen dent, homotypic cell-cell adhesion and plays an important role in main taining the normal phenotype of epithelial cells, Disruption of E-cadh erin activity in epithelial cells correlates with formation of metasta tic tumors, Decreased adhesive function may be implemented in a number of ways including: (a) decreased expression of E-cadherin; (b) mutati ons in the gene encoding E-cadherin; or (c) mutations in the genes tha t encode the catenins, proteins that link the cadherins to the cytoske leton and are essential for cadherin mediated cell-cell adhesion. In t his study, we explored the possibility that inappropriate expression o f a nonepithelial cadherin by an epithelial cell might also result in disruption of cell-cell adhesion, We showed that a squamous cell carci noma-derived cell line expressed N-cadherin and displayed a scattered fibroblastic phenotype along with decreased expression of E- and P-cad herin. Transfection of this cell line with antisense N-cadherin result ed in reversion to a normal-appearing squamous epithelial cell with in creased E- and P-cadherin expression, In addition, transfection of a n ormal-appearing squamous epithelial cell line with N-cadherin resulted in downregulation of both E- and P-cadherin and a scattered fibroblas tic phenotype. In all cases, the levels of expression of N-cadherin an d E-cadherin were inversely related to one another, In addition, we sh owed that some squamous cell carcinomas expressed N-cadherin in situ a nd those tumors expressing N-cadherin were invasive, These studies led us to propose a novel mechanism for tumorigenesis in squamous epithel ial cells; i.e., inadvertent expression of a nonepithelial cadherin.