Title: TAK1 Suppresses a NEMO-Dependent but NF-kappa B-Independent Pathway to Liver Cancer
Authors: Bettermann, Kira
Vucur, Mihael
Haybaeck, Johannes
Koppe, Christiane
Janssen, Joern
Heymann, Felix
Weber, Achim
Weiskirchen, Ralf
Liedtke, Christian
Gassler, Nikolaus
Mueller, Michael
De Vos, Rita
Wolf, Monika Julia
Boege, Yannick
Seleznik, Gitta Maria
Zeller, Nicolas
Erny, Daniel
Fuchs, Thomas
Zoller, Stefan
Cairo, Stefano
Buendia, Marie-Annick
Prinz, Marco
Akira, Shizuo
Tacke, Frank
Heikenwalder, Mathias
Trautwein, Christian
Luedde, Tom # ×
Issue Date: 18-May-2010
Publisher: Cell press
Series Title: Cancer cell vol:17 issue:5 pages:481-496
Abstract: 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-kappa B 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-kappa B-independent functions of the I kappa B-kinase (IKK)-subunit NF-kappa B essential modulator (NEMO). Therefore, TAK1 serves as a gatekeeper for a protumorigenic, NF-kappa B-independent function of NEMO in parenchymal liver cells.
ISSN: 1535-6108
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Translational Cell & Tissue Research
× corresponding author
# (joint) last author

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