Regulation and Role of GLI1 in Cutaneous Squamous Cell Carcinoma Pathogenesis

The study investigated the role of GLI1 in cutaneous squamous cell carcinoma (cSCC) and found that GLI1 expression was low and heterogeneous in cSCC tumor nests, suggesting a minor role of Hedgehog (HH) signaling in cSCC. High expression of EGFR, pS6, Ki67, and SOX9 at the tumor-stromal interface indicated a more aggressive cSCC phenotype linked to EGF/EGFR signaling. EGFR activation inhibited GLI1 expression via the MEK/ERK pathway, which did not affect cell proliferation or migration. Lower GLI1 levels were associated with increased susceptibility to chemically-induced papilloma formation in a mouse model, suggesting a complex role of GLI1 in skin tumorigenesis. The study involved 10 human cSCC biopsy specimens and six cSCC cell lines.