Sowing the Field: Loss of Dermal CSL Signaling Promotes Epithelial Cancers

In the development of nonmelanoma skin cancers (NMSC), the role of DNA mutations in keratinocytes is well established. Although dermal changes are often seen in association with NMSC, the importance of such changes has not been well understood.

Notch signaling is a cell-to-cell communication pathway that converges on the DNA-binding-protein CSL to promote keratinocyte differentiation and tumor suppression. These investigators probed CSL function in mesenchymal fibroblasts in skin by removing it in genetically engineered mice. Remarkably, within 2 to 4 months, these CSL⁻ mice spontaneously developed multifocal, atypical keratinocytic tumors resembling actinic keratosis and squamous cell carcinomas. The tumor cells did not have p53 or Ras muta…