Fig. 1: The role of Cox-2 in stem/progenitor cells during the earliest stages of cutaneous SCCs.
From: New insights into the functions of Cox-2 in skin and esophageal malignancies
a Oncogenic expression of Ras (gain-of-function) and p53 (loss-of-function) can induce papillomatous tumors from basal stem/progenitors at the interfollicular epidermis. The same oncogenic combination (Ras/p53) in hair follicle stem cells can directly induce a more invasive form of SCC, mesenchymal-like spindle cell carcinoma. Ep., epithelium; SG., sebaceous gland; HF., hair follicle; DP., dermal papilla. b Skin damage, for example, UV exposure-induced skin damage, can accelerate tumorigenesis via Cox-2 upregulation from tumor-prone stem/progenitor cells. However, cell-type-specific knockout of Cox-2 can suppress tumor formation from both epidermal basal stem/progenitors and hair follicle stem cells. Furthermore, Cox-2 inhibition can suppress the cellular plasticity of hair follicle stem cell-originating cutaneous SCCs and lead to the formation of less aggressive SCC subtypes.
