Model: Bi-directional paracrine signaling between melanoma cells and keratinocytes potentiates melanoma cell movement. Our data support a model whereby factors secreted from melanoma cells activate keratinocyte Slug, which in turn decreases Grhl1, a transcriptional activator of Dsg1. The consequent loss of Dsg1 activates ERK1/2 to increase keratinocyte CXCL1 production, which in turn promotes melanoma cell migration through activation of CXCR2.