Targeting mTORC1 May Provide Selectivity for Inhibiting Proliferation of Hair Follicle Stem/Progenitor Cells During Tumor Promotion
April 2012
in “
Cancer research
”
mTORC1 hair follicle stem/progenitor cells TPA PKC EGFR Akt rapamycin epidermal hyperplasia label-retaining cells bulge region keratinocyte populations bulge-region KSCs mammalian target of rapamycin complex 1 hair follicle stem cells 12-O-tetradecanoylphorbol-13-acetate protein kinase C epidermal growth factor receptor protein kinase B sirolimus skin thickening LRCs hair follicle bulge skin cells bulge-region keratinocyte stem cells
TLDR Blocking mTORC1 may help prevent skin cancer by stopping the growth of certain skin stem cells.
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.
