Injury prevents Ras mutant cell expansion in mosaic skin.

ABSTRACT: Healthy skin is a mosaic of wild-type and mutant clones^1,2. Although injury can cooperate with mutated Ras family proteins to promote tumorigenesis^3-12, the consequences in genetically mosaic skin are unknown. Here we show that after injury, wild-type cells suppress aberrant growth induced by oncogenic Ras. Hras^G12V/+ and Kras^G12D/+ cells outcompete wild-type cells in uninjured, mosaic tissue but their expansion is prevented after injury owing to an increase in the fraction of proliferating wild-type cells. Mechanistically, we show that, unlike Hras^G12V/+ cells, wild-type cells respond to autocrine and paracrine secretion of EGFR ligands, and this differential activation of the EGFR pathway explains the competitive switch during injury

SUBMITTER: Gallini S 

PROVIDER: S-EPMC10322723 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature