Hypothetical model. The epidermal polarity protein Par3 is an important non–cell autonomous suppressor of melanoma. (Top) Epidermal Par3 controls MC homeostasis by restricting P-cadherin–mediated KC–MC communication and thus promoting differentiated MC cytoarchitecture. (Bottom) Loss of KC Par3 leads to reduced dendritic length and increased motility, proliferation, and survival of MCs, phenotypes mediated by increased stability, and surface localization of P-cadherin in KCs. Thus, through direct KC–MC interaction, augmented P-cadherin establishes a permissive niche for MC dedifferentiation, transformation, and invasion when polarity protein function in the epidermal microenvironment is impaired (bottom, right).