HPV8 E6 Induced STAT3 Activation Leads to Hair Follicle Junctional Zone Keratinocyte Stem Cell Proliferation and Expansion in Actinic Keratoses
Studysummary This study found that HPV8-induced actinic keratoses may mechanistically involve Lrig1+ hair follicle keratinocyte stem cells, with the E6 gene promoting downstream STAT3 activity in a mouse model.
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The study investigates the cellular basis of actinic keratoses (AKs), which are precursors to squamous cell carcinoma (SCC) and basal cell carcinoma. In 79 AK samples, HPV8 was found in all cases with koilocytes (n=42) but not in those without. The research shows that HPV8 induces proliferation and expansion of Lrig1+ hair follicle junctional zone keratinocyte stem cells (HFJZKSC), mimicking AK pathology. Lineage tracing confirmed that these cells originate from Lrig1 HFJZKSC. RNA sequencing revealed that STAT3, not cMYC, is the key transcriptional regulator in HPV8-infected mice. STAT3 activation, dependent on nuclear YAP, is crucial for HFJZKSC proliferation and AK development. The E6 gene of HPV8 binds and activates STAT3, leading to ΔNP63 expression. These findings elucidate the mechanism of HPV8-associated AKs.
