Figure 6. Signaling in the Snail transgenic skin.

Expression of Snail in epidermal keratinocytes leads to a program that maintains the undifferentiated state of the transgenic cells. Snail also transcriptionally upregulates colony stimulating factor 1 (CSF1) to cause homing of macrophages (MΦ) into the skin. A subset of these macrophages is polarized along the M2/TAM (tumor associated macrophage) lineage. Together these macrophages then stimulate the local invasion of the keratinocytes into the underlying dermis. Snail expressing keratinocytes also leads to the wound-like activation of resident γδT-cells that migrate into the dermis and begin secreting IL-17. Epidermal keratinocytes respond to IL-17 by inducing expression of the cytokine IL-6, which works in a paracrine fashion to activate the transcription factor Stat3. Stat3 activation contributes to tumorigenesis by augmenting proliferation, cell survival, and angiogenesis.