Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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SHR Neuro Krebs Kardio Lipid

Grabner, B; Schramek, D; Mueller, KM; Moll, HP; Svinka, J; Hoffmann, T; Bauer, E; Blaas, L; Hruschka, N; Zboray, K; Stiedl, P; Nivarthi, H; Bogner, E; Gruber, W; Mohr, T; Zwick, RH; Kenner, L; Poli, V; Aberger, F; Stoiber, D; Egger, G; Esterbauer, H; Zuber, J; Moriggl, R; Eferl, R; Győrffy, B; Penninger, JM; Popper, H; Casanova, E.
Disruption of STAT3 signalling promotes KRAS-induced lung tumorigenesis.
Nat Commun. 2015; 6(4):6285-6285 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Kenner Lukas
Popper Helmuth
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Number of Figures: 5
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Abstract:
STAT3 is considered to play an oncogenic role in several malignancies including lung cancer; consequently, targeting STAT3 is currently proposed as therapeutic intervention. Here we demonstrate that STAT3 plays an unexpected tumour-suppressive role in KRAS mutant lung adenocarcinoma (AC). Indeed, lung tissue-specific inactivation of Stat3 in mice results in increased Kras(G12D)-driven AC initiation and malignant progression leading to markedly reduced survival. Knockdown of STAT3 in xenografted human AC cells increases tumour growth. Clinically, low STAT3 expression levels correlate with poor survival and advanced malignancy in human lung AC patients with smoking history, which are prone to KRAS mutations. Consistently, KRAS mutant lung tumours exhibit reduced STAT3 levels. Mechanistically, we demonstrate that STAT3 controls NF-κB-induced IL-8 expression by sequestering NF-κB within the cytoplasm, thereby inhibiting IL-8-mediated myeloid tumour infiltration and tumour vascularization and hence tumour progression. These results elucidate a novel STAT3-NF-κB-IL-8 axis in KRAS mutant AC with therapeutic and prognostic relevance.
Find related publications in this database (using NLM MeSH Indexing)
Adenocarcinoma - drug therapy
Animals -
Carcinogenesis -
Chromatin Immunoprecipitation -
Enzyme-Linked Immunosorbent Assay -
Gene Expression Regulation, Neoplastic - physiology
Gene Knockdown Techniques -
Heterografts -
Humans -
Immunoblotting -
In Situ Hybridization -
Interleukin-8 - metabolism
Lung Neoplasms - drug therapy
Mice -
NF-kappa B - metabolism
Proto-Oncogene Proteins p21(ras) - genetics
Real-Time Polymerase Chain Reaction -
STAT3 Transcription Factor - genetics
Signal Transduction - physiology
Statistics, Nonparametric -
Tissue Array Analysis -

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