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Here we demonstrate that STAT3 plays an unexpected tumour-suppressive role in <jats:italic>KRAS<\/jats:italic> mutant lung adenocarcinoma (AC). Indeed, lung tissue-specific inactivation of <jats:italic>Stat3<\/jats:italic> in mice results in increased <jats:italic>Kras<\/jats:italic><jats:sup>G12D<\/jats:sup>-driven AC initiation and malignant progression leading to markedly reduced survival. Knockdown of STAT3 in xenografted human AC cells increases tumour growth. Clinically, low <jats:italic>STAT3<\/jats:italic> expression levels correlate with poor survival and advanced malignancy in human lung AC patients with smoking history, which are prone to <jats:italic>KRAS<\/jats:italic> mutations. Consistently, <jats:italic>KRAS<\/jats:italic> mutant lung tumours exhibit reduced STAT3 levels. Mechanistically, we demonstrate that STAT3 controls NF-\u03baB-induced <jats:italic>IL-8<\/jats:italic> expression by sequestering NF-\u03baB within the cytoplasm, thereby inhibiting IL-8-mediated myeloid tumour infiltration and tumour vascularization and hence tumour progression. These results elucidate a novel STAT3\u2013NF-\u03baB\u2013IL-8 axis in <jats:italic>KRAS<\/jats:italic> mutant AC with therapeutic and prognostic relevance.<\/jats:p>","DOI":"10.1038\/ncomms7285","type":"journal-article","created":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T15:57:38Z","timestamp":1425398258000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":122,"title":["Disruption of STAT3 signalling promotes KRAS-induced lung tumorigenesis"],"prefix":"10.1038","volume":"6","author":[{"given":"Beatrice","family":"Grabner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Schramek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina M.","family":"Mueller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6438-9068","authenticated-orcid":false,"given":"Herwig P.","family":"Moll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmin","family":"Svinka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Hoffmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Bauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leander","family":"Blaas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natascha","family":"Hruschka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katalin","family":"Zboray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Stiedl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harini","family":"Nivarthi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edith","family":"Bogner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Gruber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Mohr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf Harun","family":"Zwick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Kenner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Poli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fritz","family":"Aberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmar","family":"Stoiber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerda","family":"Egger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Esterbauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Zuber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0918-9463","authenticated-orcid":false,"given":"Richard","family":"Moriggl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Eferl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bal\u00e1zs","family":"Gy\u0151rffy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef M.","family":"Penninger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Popper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilio","family":"Casanova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,3,3]]},"reference":[{"key":"BFncomms7285_CR1","doi-asserted-by":"publisher","first-page":"69","DOI":"10.3322\/caac.20107","volume":"61","author":"A Jemal","year":"2011","unstructured":"Jemal, A. et al. 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