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@ARTICLE{Pyczek:148820,
      author       = {J. Pyczek and N. Khizanishvili and M. Kuzyakova and S.
                      Zabel and J. Bauer and F. Nitzki and S. Emmert and M. P.
                      Schön and P. Boukamp$^*$ and H.-U. Schildhaus and A. Uhmann
                      and H. Hahn},
      title        = {{R}egulation and {R}ole of {GLI}1 in {C}utaneous {S}quamous
                      {C}ell {C}arcinoma {P}athogenesis.},
      journal      = {Frontiers in genetics},
      volume       = {10},
      issn         = {1664-8021},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DKFZ-2020-00012},
      pages        = {1185},
      year         = {2019},
      abstract     = {Cutaneous squamous cell carcinoma (cSCC) is the second most
                      common skin tumor in humans. Although current therapies are
                      sufficient to clear the tumor in many cases, the overall
                      risk of cSCC metastasis is still $5\%.$ Alternative
                      treatment options could help to overcome this situation.
                      Here we focused on the role of the Hedgehog (HH) signaling
                      pathway and its interplay with epidermal growth factor
                      receptor (EGFR) signaling in cSCC. The analyses revealed
                      that, despite lack of Sonic HH (SHH) expression, a subset of
                      human cSCC can express GLI1, a marker for active HH
                      signaling, within distinct tumor areas. In contrast, all
                      tumors strongly express EGFR and the hair follicle stem cell
                      marker SOX9 at the highly proliferative tumor-stroma
                      interface, whereas central tumor regions with a more
                      differentiated stratum spinosum cell type lack both EGFR and
                      SOX9 expression. In vitro experiments indicate that
                      activation of EGFR signaling in the human cSCC cell lines
                      SCL-1, MET-1, and MET-4 leads to GLI1 inhibition via the
                      MEK/ERK axis without affecting cellular proliferation. Of
                      note, EGFR activation also inhibits cellular migration of
                      SCL-1 and MET-4 cells. Because proliferation and migration
                      of the cells is also not altered by a GLI1 knockdown, GLI1
                      is apparently not involved in processes of aggressiveness in
                      established cSCC tumors. In contrast, our data rather
                      suggest a negative correlation between Gli1 expression level
                      and cSCC formation because skin of Ptch +/- mice with
                      slightly elevated Gli1 expression levels is significantly
                      less susceptible to chemically-induced cSCC formation
                      compared to murine wildtype skin. Although not yet formally
                      validated, these data open the possibility that GLI1 (and
                      thus HH signaling) may antagonize cSCC initiation and is not
                      involved in cSCC aggressiveness, at least in a subset of
                      cSCC.},
      cin          = {A110},
      ddc          = {570},
      cid          = {I:(DE-He78)A110-20160331},
      pnm          = {311 - Signalling pathways, cell and tumor biology
                      (POF3-311)},
      pid          = {G:(DE-HGF)POF3-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:31867038},
      pmc          = {pmc:PMC6904360},
      doi          = {10.3389/fgene.2019.01185},
      url          = {https://inrepo02.dkfz.de/record/148820},
}