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[Cancer Research 61, 3819-3825, May 1, 2001]
© 2001 American Association for Cancer Research

Tumor Biology

N-Cadherin-mediated Intercellular Interactions Promote Survival and Migration of Melanoma Cells1

Gang Li, Kapaettu Satyamoorthy and Meenhard Herlyn2

The Wistar Institute [G. L., K. S., M. H.], and Program of Cell and Molecular Biology, Biomedical Graduate Studies, University of Pennsylvania School of Medicine [G. L.], Philadelphia, Pennsylvania 19104

During melanoma development, loss of functional E-cadherin accompanies gain of expression of N-cadherin. The present study was carried out to investigate the functional significance of N-cadherin in melanoma cells. N-Cadherin mediated homotypic aggregation among melanoma cells as well as heterotypic adhesion of melanoma cells to dermal fibroblasts and vascular endothelial cells. Blocking of N-cadherin-mediated intercellular interaction by N-cadherin-specific antibodies increased the number of cells undergoing apoptosis. N-Cadherin-mediated cell adhesion-activated antiapoptotic protein Akt/PKB and subsequently increased ß-catenin and inactivated the proapoptotic factor Bad. Furthermore, N-cadherin promoted migration of melanocytic cells over dermal fibroblasts, suggesting that N-cadherin may also play a role in metastasis. Together, these results indicate that the cadherin subtype switching from E- to N-cadherin during melanoma development not only frees melanocytic cells from the control by keratinocytes but also provides growth and possibly metastatic advantages to melanoma cells.




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