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 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.
Li
G
G
The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
Satyamoorthy
K
K
Herlyn
M
M
D022005:Adherens Junctions / Q000502:physiology; D015820:Cadherins / Q000096:biosynthesis / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D004789:Enzyme Activation; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008545:Melanoma / Q000378:metabolism / Q000473:pathology* / Q000556:secondary; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction / Q000502:physiology; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000556:secondary; D014407:Tumor Cells, Cultured
D015820:Cadherins; D011518:Proto-Oncogene Proteins; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt