Reversal of melanocytic malignancy by keratinocytes is an E-cadherin-mediated process overriding beta-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-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.
Li
Gang
G
The Wistar Institute, Philadelphia, PA 19104, USA.
Fukunaga
Mizuho
M
Herlyn
Meenhard
M
D015703:Antigens, CD; D051929:CD146 Antigen; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000235:genetics; D002450:Cell Communication / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D018920:Coculture Techniques; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D008544:Melanocytes / Q000378:metabolism*; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D019006:Neural Cell Adhesion Molecules; D017434:Protein Structure, Tertiary / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D015534:Trans-Activators / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D051176:beta Catenin
D015703:Antigens, CD; D051929:CD146 Antigen; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; C497902:MCAM protein, human; D008562:Membrane Glycoproteins; D019006:Neural Cell Adhesion Molecules; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D051176:beta Catenin