The morphogenic function of E-cadherin-mediated adherens junctions in epithelial ovarian carcinoma formation and progression.

Abstract

E-cadherin expression is unusually regulated in epithelial ovarian carcinoma. It is not expressed in poorly cohesive ovarian surface epithelial (OSE) target cells, but is expressed in cohesive pre-malignant lesions and in highly cohesive, well-differentiated tumors where it is membrane associated, presumably in adherens junctions. E-cadherin expression is subsequently suppressed, or its function is disrupted, in late-stage invasive tumors. Here, we observed that increased E-cadherin expression in ovarian carcinoma cells was associated with increased E-cadherin promoter activity, increased adherens junction formation, decreased beta-catenin signaling-dependent LEF-1 activity, and the generation of cohesive spheroids in basement membrane gel culture. Forced expression of wild-type E-cadherin in immortalized OSE cells initiated adherens junction formation, decreased LEF-1 activity, decreased the mesenchymal migration that is a characteristic of OSE cells that have been maintained in monolayer culture, and induced the formation of cohesive spheroids in basement membrane gels. Conversely, forced expression of a dominant-negative E-cadherin mutant in ovarian carcinoma cells disrupted adherens junctions, increased mesenchymal cell migration, and prevented spheroidal morphogenesis without altering LEF-1 signaling. Therefore, in addition to suppressing late-stage tumor progression, E-cadherin-mediated adherens junctions may also contribute to the initial emergence of a cohesive morphogenic phenotype that is a hallmark of differentiated epithelial ovarian carcinoma.

• Authors: Colleen Wu, Jane Cipollone, Sarah Maines-Bandiera, Clara Tan, Aly Karsan, Nelly Auersperg, Calvin D Roskelley
• Journal: Differentiation; research in biological diversity (Differentiation) Vol. 76 Issue 2 Pg. 193-205 (Feb 2008) ISSN: 1432-0436 [Electronic] England
• PMID: 17608733 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cadherins
• Lymphoid Enhancer-Binding Factor 1

Topics

• Adherens Junctions (metabolism)
• Cadherins (metabolism)
• Carcinoma (metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation
• Epithelial Cells (cytology)
• Female
• Humans
• Lymphoid Enhancer-Binding Factor 1 (metabolism)
• Ovarian Neoplasms (metabolism, pathology)