Regulation and Role of GLI1 in Cutaneous Squamous Cell Carcinoma Pathogenesis

December 2019 in “ Frontiers in genetics ”

Joanna Pyczek, Natalia Khizanishvili, Maria Kuzyakova, Sebastian Zabel, Julia Bauer, Frauke Nitzki, Steffen Emmert, Michael P. Schön, Petra Boukamp, Hans Ulrich Schildhaus, Anja Uhmann, Heidi Hahn

cutaneous squamous cell carcinoma GLI1 Hedgehog signaling EGFR pS6 Ki67 SOX9 MEK/ERK pathway papilloma skin tumorigenesis cSCC epidermal growth factor receptor mitogen-activated protein kinase/extracellular signal-regulated kinase pathway

TLDR GLI1 might protect against the start of skin cancer and is not linked to cancer severity.

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.

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