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@ARTICLE{Kirschberg:176895,
      author       = {M. Kirschberg and A. S. Syed and H. G. Dönmez and S.
                      Heuser and A. Wilbrand-Hennes and A. Alonso$^*$ and M.
                      Hufbauer and B. Akgül},
      title        = {{N}ovel {I}nsights {I}nto {C}ellular {C}hanges in
                      {HPV}8-{E}7 {P}ositive {K}eratinocytes: {A} {T}ranscriptomic
                      and {P}roteomic {A}nalysis.},
      journal      = {Frontiers in microbiology},
      volume       = {12},
      issn         = {1664-302X},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DKFZ-2021-02137},
      pages        = {672201},
      year         = {2021},
      abstract     = {Human papillomavirus type 8 (HPV8) is associated with the
                      development of non-melanoma skin cancer. In the past we
                      already delved into the mechanisms involved in keratinocyte
                      invasion, showing that the viral E7 oncoprotein is a key
                      player that drives invasion of basal keratinocytes
                      controlled by the extracellular protein fibronectin. To
                      unravel further downstream effects in E7 expressing
                      keratinocytes we now aimed at characterizing gene and
                      protein/phosphoprotein alterations to narrow down on key
                      cellular targets of HPV8-E7. We now show that gene
                      expression of GADD34 and GDF15 are strongly activated in the
                      presence of E7 in primary human keratinocytes. Further
                      analyses of fibronectin-associated factors led to the
                      identification of the Src kinase family members Fyn and Lyn
                      being aberrantly activated in the presence of HPV8-E7.
                      Phospho-proteomics further revealed that E7 not only targets
                      cell polarity and cytoskeletal organization, but also
                      deregulates the phosphorylation status of nuclear proteins
                      involved in DNA damage repair and replication. Many of these
                      differentially phosphorylated proteins turned out to be
                      targets of Fyn and Lyn. Taken together, by using unbiased
                      experimental approaches we have now arrived at a deeper
                      understanding on how fibronectin may affect the signaling
                      cascades in HPV8 positive keratinocytes, which may be key
                      for skin tumorigenesis and that may also aid in the
                      development of novel therapeutic approaches for
                      betaHPV-mediated cancers.},
      keywords     = {E7 oncoprotein (Other) / betapapillomavirus (Other) /
                      fibronectin (Other) / keratinocyte invasion (Other) / skin
                      cancer (Other)},
      cin          = {F050},
      ddc          = {570},
      cid          = {I:(DE-He78)F050-20160331},
      pnm          = {316 - Infektionen, Entzündung und Krebs (POF4-316)},
      pid          = {G:(DE-HGF)POF4-316},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34552568},
      pmc          = {pmc:PMC8450583},
      doi          = {10.3389/fmicb.2021.672201},
      url          = {https://inrepo02.dkfz.de/record/176895},
}