Targeted Disruption of Stat3 Reveals a Major Role for Follicular Stem Cells in Skin Tumor Initiation

October 2009 in “ Cancer research ”

Dae Joon Kim, Ken Kataoka, Dharanija Rao, Kaoru Kiguchi, George Cotsarelis, John DiGiovanni

Stat3 keratinocyte stem cells bulge region hair follicles apoptosis Ha-ras mutations papillomas skin tumor formation KSCs hair follicle stem cells

TLDR Disrupting Stat3 in hair follicle stem cells greatly reduces skin tumor formation.

The study demonstrated that Stat3 was crucial for the survival of DNA-damaged keratinocyte stem cells (KSCs) in the bulge region of hair follicles during skin tumor initiation in mice. Disrupting Stat3 in these cells led to increased apoptosis, reduced Ha-ras mutations, and an ~80% reduction in skin tumor formation. Only 30% of Stat3-deficient mice developed papillomas compared to 100% of control mice, indicating that bulge region KSCs were primary targets for tumor initiation. These findings suggested that targeting Stat3 in KSCs could be a viable strategy for preventing skin cancer.

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