Targeting mTORC1 May Provide Selectivity for Inhibiting Proliferation of Hair Follicle Stem/Progenitor Cells During Tumor Promotion

The study investigated the role of mTORC1 signaling in skin tumor promotion and hair follicle stem/progenitor cell proliferation using mouse models. Activation of mTORC1 by TPA was shown to be mediated by PKC, EGFR, and Akt. Rapamycin effectively inhibited TPA-induced epidermal hyperplasia and tumor promotion in both wild-type and transgenic mice overexpressing Akt1. Additionally, rapamycin prevented the migration and proliferation of label-retaining cells (LRCs) from hair follicles, keeping them in the bulge region, which is crucial for tumor development. These findings suggested that targeting mTORC1 could be a potential strategy for preventing epithelial carcinogenesis by inhibiting the proliferation of keratinocyte populations, including bulge-region KSCs.