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Bettermann, K.* ; Vucur, M.* ; Haybaeck, J.* ; Koppe, C.* ; Janssen, J.* ; Heymann, F.* ; Weber, A.* ; Weiskirchen, R.* ; Liedtke, C.* ; Gassler, N.* ; Müller, M.* ; de Vos, R.* ; Wolf, M.J.* ; Boege, Y.* ; Seleznik, G.M.* ; Zeller, N.* ; Erny, D.* ; Fuchs, T.* ; Zoller, S.* ; Cairo, S.* ; Buendia, M.A.* ; Prinz, M.* ; Akira, S.* ; Tacke, F.* ; Heikenwälder, M. ; Trautwein, C.* ; Luedde, T.*

TAK1 suppresses a NEMO-dependent but NF-κB-independent pathway to liver cancer.

Cancer Cell 17, 481-496 (2010)
DOI Verlagsversion bestellen
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
The MAP3-kinase TGF-beta-activated kinase 1 (TAK1) critically modulates innate and adaptive immune responses and connects cytokine stimulation with activation of inflammatory signaling pathways. Here, we report that conditional ablation of TAK1 in liver parenchymal cells (hepatocytes and cholangiocytes) causes hepatocyte dysplasia and early-onset hepatocarcinogenesis, coinciding with biliary ductopenia and cholestasis. TAK1-mediated cancer suppression is exerted through activating NF-kappaB in response to tumor necrosis factor (TNF) and through preventing Caspase-3-dependent hepatocyte and cholangiocyte apoptosis. Moreover, TAK1 suppresses a procarcinogenic and pronecrotic pathway, which depends on NF-kappaB-independent functions of the I kappaB-kinase (IKK)-subunit NF-kappaB essential modulator (NEMO). Therefore, TAK1 serves as a gatekeeper for a protumorigenic, NF-kappaB-independent function of NEMO in parenchymal liver cells.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Hepatocellular-carcinoma; Chemical hepatocarcinogenesis; Protein-kinases; Activation; Mice; Inflammation; Injury; Cell; JNK; Hepatocytes
ISSN (print) / ISBN 1535-6108
e-ISSN 1878-3686
Zeitschrift Cancer Cell
Quellenangaben Band: 17, Heft: 5, Seiten: 481-496 Artikelnummer: , Supplement: ,
Verlag Cell Press
Verlagsort Cambridge, Mass.
Begutachtungsstatus Peer reviewed