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Pencik, Jan; Schlederer, Michaela; Gruber, Wolfgang; Unger, Christine; Walker, Steven M.; Chalaris, Athena; Marié, Isabelle J.; Hassler, Melanie R.; Javaheri, Tahereh; Aksoy, Osman; Blayney, Jaine K.; Prutsch, Nicole; Skucha, Anna; Herac, Merima; Krämer, Oliver H.; Mazal, Peter; Grebien, Florian; Egger, Gerda; Poli, Valeria; Mikulits, Wolfgang; Eferl, Robert; Esterbauer, Harald; Kennedy, Richard; Fend, Falko; [...]

STAT3 regulated ARF expression suppresses prostate cancer metastasis

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  • Medientyp: E-Artikel
  • Titel: STAT3 regulated ARF expression suppresses prostate cancer metastasis
  • Beteiligte: Pencik, Jan; Schlederer, Michaela; Gruber, Wolfgang; Unger, Christine; Walker, Steven M.; Chalaris, Athena; Marié, Isabelle J.; Hassler, Melanie R.; Javaheri, Tahereh; Aksoy, Osman; Blayney, Jaine K.; Prutsch, Nicole; Skucha, Anna; Herac, Merima; Krämer, Oliver H.; Mazal, Peter; Grebien, Florian; Egger, Gerda; Poli, Valeria; Mikulits, Wolfgang; Eferl, Robert; Esterbauer, Harald; Kennedy, Richard; Fend, Falko; [...]
  • Erschienen: Springer Science and Business Media LLC, 2015
  • Erschienen in: Nature Communications
  • Sprache: Englisch
  • DOI: 10.1038/ncomms8736
  • ISSN: 2041-1723
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>Prostate cancer (PCa) is the most prevalent cancer in men. Hyperactive STAT3 is thought to be oncogenic in PCa. However, targeting of the IL-6/STAT3 axis in PCa patients has failed to provide therapeutic benefit. Here we show that genetic inactivation of <jats:italic>Stat3</jats:italic> or <jats:italic>IL-6</jats:italic> signalling in a <jats:italic>Pten</jats:italic>-deficient PCa mouse model accelerates cancer progression leading to metastasis. Mechanistically, we identify p19<jats:sup>ARF</jats:sup> as a direct Stat3 target. Loss of Stat3 signalling disrupts the ARF–Mdm2–p53 tumour suppressor axis bypassing senescence. Strikingly, we also identify <jats:italic>STAT3</jats:italic> and <jats:italic>CDKN2A</jats:italic> mutations in primary human PCa. <jats:italic>STAT3</jats:italic> and <jats:italic>CDKN2A</jats:italic> deletions co-occurred with high frequency in PCa metastases. In accordance, loss of STAT3 and p14<jats:sup>ARF</jats:sup> expression in patient tumours correlates with increased risk of disease recurrence and metastatic PCa. Thus, STAT3 and ARF may be prognostic markers to stratify high from low risk PCa patients. Our findings challenge the current discussion on therapeutic benefit or risk of IL-6/STAT3 inhibition.</jats:p>
  • Zugangsstatus: Freier Zugang