Hedgehog-Wnt Interactions during Pathologic Epithelial Bud Development and Skin Tumorigenesis.

The study explored the interactions between Hedgehog (Hh) and Wnt/beta-catenin signaling pathways in skin tumorigenesis, particularly in basal cell carcinoma (BCC) and basaloid follicular hamartoma. It was found that while Hh signaling is constitutively active in these tumors, the development of epithelial buds and hamartomas also requires canonical Wnt/beta-catenin signaling. This was demonstrated by the inhibition of these developments through the overexpression of the Wnt antagonist Dkk1 in mice, which did not affect Hh signaling. The research highlighted the necessity of Wnt signaling for Hh-driven tumorigenesis and suggested Wnt ligands as potential therapeutic targets. Additionally, the study showed that Hh signaling could reactivate hair follicle growth and melanogenesis, processes typically regulated by Wnt signaling, further emphasizing the critical role of Wnt in mediating Hh pathway effects in skin neoplasms.