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Crnčec, Ilija; Modak, Madhura; Gordziel, Claire; Svinka, Jasmin; Scharf, Irene; Moritsch, Stefan; Pathria, Paulina; Schlederer, Michaela; Kenner, Lukas; Timelthaler, Gerald; Müller, Mathias; Strobl, Birgit; Casanova, Emilio; Bayer, Editha; Mohr, Thomas; Stöckl, Johannes; Friedrich, Karlheinz; Eferl, Robert

STAT1 is a sex‐specific tumor suppressor in colitis‐associated colorectal cancer

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  • Media type: E-Article
  • Title: STAT1 is a sex‐specific tumor suppressor in colitis‐associated colorectal cancer
  • Contributor: Crnčec, Ilija; Modak, Madhura; Gordziel, Claire; Svinka, Jasmin; Scharf, Irene; Moritsch, Stefan; Pathria, Paulina; Schlederer, Michaela; Kenner, Lukas; Timelthaler, Gerald; Müller, Mathias; Strobl, Birgit; Casanova, Emilio; Bayer, Editha; Mohr, Thomas; Stöckl, Johannes; Friedrich, Karlheinz; Eferl, Robert
  • imprint: Wiley, 2018
  • Published in: Molecular Oncology
  • Language: English
  • DOI: 10.1002/1878-0261.12178
  • ISSN: 1574-7891; 1878-0261
  • Keywords: Cancer Research ; Genetics ; Molecular Medicine ; General Medicine ; Oncology
  • Origination:
  • Footnote:
  • Description: <jats:p>The interferon‐inducible transcription factor STAT1 is a tumor suppressor in various malignancies. We investigated sex‐specific STAT1 functions in colitis and colitis‐associated colorectal cancer (CRC) using mice with specific STAT1 deletion in intestinal epithelial cells (STAT1<jats:sup>∆IEC</jats:sup>). Male but not female STAT1<jats:sup>∆IEC</jats:sup> mice were more resistant to DSS‐induced colitis than sex‐matched STAT1<jats:sup>flox/flox</jats:sup> controls and displayed reduced intraepithelial infiltration of CD8<jats:sup>+</jats:sup> TCRαβ<jats:sup>+</jats:sup> granzyme B<jats:sup>+</jats:sup> T cells. Moreover, DSS treatment failed to induce expression of T‐cell‐attracting chemokines in intestinal epithelial cells of male but not of female STAT1<jats:sup>∆IEC</jats:sup> mice. Application of the AOM‐DSS protocol for induction of colitis‐associated CRC resulted in increased intestinal tumor load in male but not in female STAT1<jats:sup>∆IEC</jats:sup> mice. A sex‐specific stratification of human CRC patients corroborated the data obtained in mice and revealed that reduced tumor cell‐intrinsic nuclear STAT1 protein expression is a poor prognostic factor in men but not in women. These data demonstrate that epithelial STAT1 is a male‐specific tumor suppressor in CRC of mice and humans.</jats:p>
  • Access State: Open Access