SOX2 confers tumour permissiveness in a specific skin progenitor population.

ABSTRACT: The continuous renewal of the skin relies on stem and progenitor cells, yet their differential susceptibility to oncogenic mutations in cutaneous squamous cell carcinoma (cSCC) remains unclear. Rapid cSCC develops in melanoma patients on BRAF inhibitors due to paradoxical MAPK activation. To model this in mice, we use two complementary approaches: HRAS^G12V with a BRAF inhibitor to mimic paradoxical MAPK activation, and BRAF^V600E, which drives MAPK hyperactivation without further treatment. We target these mutations to the interfollicular stem and differentiation-committed progenitors of the basal epidermis. While stem cells rapidly form tumours, progenitors exhibit long-latency resistance despite retaining mutations and repopulating the basal layer. Ultimately, both p

SUBMITTER: Centeno PP 

PROVIDER: S-EPMC12789432 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature