Homeostases of epidermis and hair follicle, and development of basal cell carcinoma

Abstract

Hedgehog signaling (Hh) plays a critical role in embryogenesis. On the other hand, its overactivity may cause basal cell carcinoma (BCC), the most common human cancer. Further, epidermal and hair follicle homeostases may have a key role in the development of BCC. This article describes the importance of different signaling pathways in the different stages of the two processes. The description of the homeostases brought up the importance of the Notch signaling along with the sonic hedgehog (Shh) and the Wnt pathways. Loss of the Notch signaling adversely affects the late stages of hair follicle formation and allows the bulge cells in the hair follicles to take the fate of the keratinocytes in the interfollicular epidermis. Further, the loss of Notch activity upregulates the Shh and Wnt activities, adversely affecting the homeostases. Notably, the Notch signaling is suppressed in BCC, and the peripheral BCC cells, which have low Notch activity, show drug resistance in comparison to the interior suprabasal BCC cells, which have high Notch activity.

Keywords: Basal cell carcinoma; Dermal condensate; Dermal papilla; Eda; Edar; Epidermal placode; Hair follicle; Hair follicle differentiation; Hair follicle homeostasis; Hair placode; Hedgehog; Notch; Skin; Skin differentiation; Skin homeostasis; Sonic hedgehog; Wnt.