Expression of N-cadherin by human squamous carcinoma cells induces a scattered fibroblastic phenotype with disrupted cell-cell adhesion

Shahidul Islam, Thomas E. Carey, Gregory T. Wolf, Margaret J. Wheelock, Keith R Johnson

Research output: Contribution to journalArticle

262 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1643-1654
Number of pages12
JournalJournal of Cell Biology
Volume135
Issue number6
DOIs
StatePublished - Dec 1 1996

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Cadherins
Cell Adhesion
Squamous Cell Carcinoma
Phenotype
Epithelial Cells
Cell Line
Transfection
Catenins
Mutation
Cytoskeleton

ASJC Scopus subject areas

  • Cell Biology

Cite this

Expression of N-cadherin by human squamous carcinoma cells induces a scattered fibroblastic phenotype with disrupted cell-cell adhesion. / Islam, Shahidul; Carey, Thomas E.; Wolf, Gregory T.; Wheelock, Margaret J.; Johnson, Keith R.

In: Journal of Cell Biology, Vol. 135, No. 6, 01.12.1996, p. 1643-1654.

Research output: Contribution to journalArticle

Islam, Shahidul ; Carey, Thomas E. ; Wolf, Gregory T. ; Wheelock, Margaret J. ; Johnson, Keith R. / Expression of N-cadherin by human squamous carcinoma cells induces a scattered fibroblastic phenotype with disrupted cell-cell adhesion. In: Journal of Cell Biology. 1996 ; Vol. 135, No. 6. pp. 1643-1654.
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