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@ARTICLE{Strobel:285668,
      author       = {T. Strobel$^*$ and M. Weber$^*$ and N. Heber$^*$ and A.
                      Holzer$^*$ and K. Hoppe-Seyler$^*$ and F. Hoppe-Seyler$^*$},
      title        = {{R}evisiting the role of endogenous {STAT}3 in
                      {HPV}-positive cervical cancer cells.},
      journal      = {Journal of medical virology},
      volume       = {95},
      number       = {11},
      issn         = {0146-6615},
      address      = {Bognor Regis [u.a.]},
      publisher    = {Wiley},
      reportid     = {DKFZ-2023-02491},
      pages        = {e29230},
      year         = {2023},
      note         = {#EA:F065#LA:F065# / 2023 Nov;95(11):e29230},
      abstract     = {Novel treatment options for human papillomavirus
                      (HPV)-induced cancers are urgently required. The oncogenic
                      transcription factor signal transducer and activator of
                      transcription 3 (STAT3) is considered to be constitutively
                      active in HPV-positive cervical cancer cells and essential
                      for their proliferation. Moreover, STAT3 was reported to
                      undergo mutually stimulatory interactions with the HPV E6/E7
                      oncogenes. Thus, inhibiting STAT3 in HPV-positive cancer
                      cells is under discussion to provide a powerful novel
                      therapeutic strategy. We here show that the antifungal drug
                      ciclopirox destabilizes the STAT3 protein by acting as an
                      iron chelator. However, by exploring the functional
                      consequences of STAT3 inhibition in HPV-positive cancer
                      cells, we obtained several unexpected results. Chemical
                      STAT3 inhibitors heterogeneously affect cervical cancer cell
                      proliferation and those which act antiproliferative also
                      block the growth of STAT3 knockout cells, indicating
                      induction of off-target effects. In contrast to several
                      chemical inhibitors, genetic inhibition of STAT3 expression
                      by either RNA interference or the CRISPR/Cas9 method does
                      not appreciably affect cervical cancer cell proliferation.
                      Transcriptome analyses indicate that blocking STAT3
                      expression in HPV-positive cancer cells has very limited
                      effects on putative STAT3 target genes. Although the
                      targeted inhibition of specific growth-promoting signaling
                      pathways leads to a feedback activation of STAT3 in cervical
                      cancer cells via Janus kinase 1/2, this does not lead to
                      treatment resistance. Moreover, we did not obtain
                      experimental evidence for a STAT3-linked activation of HPV
                      E6/E7 oncogene expression or, vice versa, an E6/E7-dependent
                      activation of STAT3, at endogenous conditions in cervical
                      cancer cells. Collectively, these findings question the
                      essential role of STAT3 in cervical cancer cell
                      proliferation and the strategy to inhibit STAT3 in these
                      cells for therapeutic purposes.},
      keywords     = {MEK (Other) / PI3K (Other) / STAT3 (Other) / cervical
                      cancer (Other) / ciclopirox (Other) / human papillomavirus
                      (Other)},
      cin          = {F065},
      ddc          = {610},
      cid          = {I:(DE-He78)F065-20160331},
      pnm          = {316 - Infektionen, Entzündung und Krebs (POF4-316)},
      pid          = {G:(DE-HGF)POF4-316},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38009614},
      doi          = {10.1002/jmv.29230},
      url          = {https://inrepo02.dkfz.de/record/285668},
}