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1: Cancer Res. 2001 May 1;61(9):3819-25.
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N-cadherin-mediated intercellular interactions promote survival and migration of melanoma cells.

Li G, Satyamoorthy K, Herlyn M.

The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.

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 beta-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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PMID: 11325858 [PubMed - indexed for MEDLINE]