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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 PMC
Open Access Green as soon as Postprint is submitted to ZB.
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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Publication type Article: Journal article
Document type Scientific Article
Keywords Hepatocellular-carcinoma; Chemical hepatocarcinogenesis; Protein-kinases; Activation; Mice; Inflammation; Injury; Cell; JNK; Hepatocytes
Language english
Publication Year 2010
HGF-reported in Year 2010
ISSN (print) / ISBN 1535-6108
e-ISSN 1878-3686
Journal Cancer Cell
Quellenangaben Volume: 17, Issue: 5, Pages: 481-496 Article Number: , Supplement: ,
Publisher Cell Press
Publishing Place Cambridge, Mass.
Reviewing status Peer reviewed
Institute(s) Institute of Virology (VIRO)
POF-Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s) Immune Response and Infection
PSP Element(s) G-551600-001
PubMed ID 20478530
DOI 10.1016/j.ccr.2010.03.021
Erfassungsdatum 2010-12-31
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