Reversal of melanocytic malignancy by keratinocytes is an E-cadherin-mediated process overriding β-catenin signaling

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-α-catenin fusion protein were functional in mediating cell adhesion, downregulating MCAM4 in coculture, and inhibiting proliferation regardless of β-catenin expression levels and activation status. In contrast, cytoplasmic domain-deleted (E-cadΔCYT) 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 β-catenin.