Reversal of melanocytic malignancy by keratinocytes is an E-cadherin-mediated process overriding beta-catenin signaling |
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Authors: | Li Gang Fukunaga Mizuho Herlyn Meenhard |
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Institution: | The Wistar Institute, Philadelphia, PA 19104, USA. |
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Abstract: | Loss of E-cadherin in melanoma cells frees them from keratinocytes-mediated proliferation and phenotypic control, which can be restored by forced E-cadherin expression. In this study, E-cadherin and its derivatives were introduced into metastatic melanoma line 1205Lu. E-cadherin and E-cadherin-alpha-catenin fusion protein were functional in mediating cell adhesion, downregulating MCAM(4) in coculture, and inhibiting proliferation regardless of beta-catenin expression levels and activation status. In contrast, cytoplasmic domain-deleted (E-cadDeltaCYT) derivative was not able to reverse malignancy. The results indicate that E-cadherin-mediated cell adhesion is required for keratinocyte-mediated control of melanocytic cells, which can override proliferative activity of beta-catenin. |
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Keywords: | E-cadherin β-Catenin Melanoma Keratinocyte MCAM |
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