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-dependent, homotypic cell-cell adhesion and plays an important role in maintaining the normal phenotype of epithelial cells. Disruption of E-cadherin activity in epithelial cells correlates with formation of metastatic tumors. Decreased adhesive function may be implemented in a number of ways including: (a) decreased expression of E-cadherin; (b) mutations in the gene encoding E-cadherin; or (c) mutations in the genes that encode the catenins, proteins that link the cadherins to the cytoskeleton and are essential for cadherin mediated cell-cell adhesion. In this study, we explored the possibility that inappropriate expression of a nonepithelial cadherin by an epithelial cell might also result in disruption of cell-cell adhesion. We showed that a squamous cell carcinoma-derived cell line expressed N-cadherin and displayed a scattered fibroblastic phenotype along with decreased expression of E- and P-cadherin. Transfection of this cell line with antisense N-cadherin resulted in reversion to a normal-appearing squamous epithelial cell with increased E- and P-cadherin expression. In addition, transfection of a normal-appearing squamous epithelial cell line with N-cadherin resulted in downregulation of both E- and P-cadherin and a scattered fibroblastic phenotype. In all cases, the levels of expression of N-cadherin and E-cadherin were inversely related to one another. In addition, we showed that some squamous cell carcinomas expressed N-cadherin in situ and those tumors expressing N-cadherin were invasive. These studies led us to propose a novel mechanism for tumorigenesis in squamous epithelial cells; i.e., inadvertent expression of a nonepithelial cadherin.
Islam
S
S
Department of Biology, University of Toledo, Ohio 43606, USA.
Carey
T E
TE
Wolf
G T
GT
Wheelock
M J
MJ
Johnson
K R
KR
D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002448:Cell Adhesion; D002454:Cell Differentiation; D016373:DNA, Antisense / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology*; D006801:Humans; D009361:Neoplasm Invasiveness; D010641:Phenotype; D014162:Transfection; D014407:Tumor Cells, Cultured
D015820:Cadherins; D016373:DNA, Antisense