N-cadherin-mediated intercellular interactions promote survival and migration of melanoma cells

During melanoma development, loss of functional E-cadherin accompanies gain of expression of N-cadherin, The present study was carried out to investig ate the functional significance of N-cadherin in melanoma cells. N-Cadherin mediated homotypic aggregation among melanoma cells as well as heterotypic adhesion of melanoma tells to dermal fibroblasts and vascular endothelial cells. Blocking of N-cadherin-mediated intercellular interaction by N-cadhe rin-specific antibodies Increased the number of cells undergoing apoptosis, N-Cadherin-mediated cell adhesion-activated antiapoptotic protein Akt/PKB and subsequently increased beta -catenin and inactivated the proapoptotic f actor 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 swi tching from E- to N-cadherin during melanoma development not only frees mel anocytic cells from the control by keratinocytes but also provides growth a nd possibly metastatic advantages to melanoma cells.