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

G. Li, K. Satyamoorthy, M. Herlyn

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    376 Citations (Scopus)

    Abstract

    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 β-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.

    Original languageEnglish
    Pages (from-to)3819-3825
    Number of pages7
    JournalCancer Research
    Volume61
    Issue number9
    Publication statusPublished - 01-05-2001

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    All Science Journal Classification (ASJC) codes

    • Cancer Research
    • Oncology

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