%0 Journal Article
%A Boege, Yannick
%A Malehmir, Mohsen
%A Healy, Marc E
%A Bettermann, Kira
%A Lorentzen, Anna
%A Vucur, Mihael
%A Ahuja, Akshay K
%A Böhm, Friederike
%A Mertens, Joachim C
%A Shimizu, Yutaka
%A Frick, Lukas
%A Remouchamps, Caroline
%A Mutreja, Karun
%A Kähne, Thilo
%A Sundaravinayagam, Devakumar
%A Wolf, Monika J
%A Rehrauer, Hubert
%A Koppe, Christiane
%A Speicher, Tobias
%A Padrissa-Altés, Susagna
%A Maire, Renaud
%A Schattenberg, Jörn M
%A Jeong, Ju-Seong
%A Liu, Lei
%A Zwirner, Stefan
%A Boger, Regina
%A Hüser, Norbert
%A Davis, Roger J
%A Müllhaupt, Beat
%A Moch, Holger
%A Schulze-Bergkamen, Henning
%A Clavien, Pierre-Alain
%A Werner, Sabine
%A Borsig, Lubor
%A Luther, Sanjiv A
%A Jost, Philipp J
%A Weinlich, Ricardo
%A Unger, Kristian
%A Behrens, Axel
%A Hillert, Laura
%A Dillon, Christopher
%A Di Virgilio, Michela
%A Wallach, David
%A Dejardin, Emmanuel
%A Zender, Lars
%A Naumann, Michael
%A Walczak, Henning
%A Green, Douglas R
%A Lopes, Massimo
%A Lavrik, Inna
%A Luedde, Tom
%A Heikenwalder, Mathias
%A Weber, Achim
%T A Dual Role of Caspase-8 in Triggering and Sensing Proliferation-Associated DNA Damage, a Key Determinant of Liver Cancer Development.
%J Cancer cell
%V 32
%N 3
%@ 1535-6108
%C Cambridge, Mass.
%I Cell Press
%M DKFZ-2017-04329
%P 342 - 359.e10
%D 2017
%X Concomitant hepatocyte apoptosis and regeneration is a hallmark of chronic liver diseases (CLDs) predisposing to hepatocellular carcinoma (HCC). Here, we mechanistically link caspase-8-dependent apoptosis to HCC development via proliferation- and replication-associated DNA damage. Proliferation-associated replication stress, DNA damage, and genetic instability are detectable in CLDs before any neoplastic changes occur. Accumulated levels of hepatocyte apoptosis determine and predict subsequent hepatocarcinogenesis. Proliferation-associated DNA damage is sensed by a complex comprising caspase-8, FADD, c-FLIP, and a kinase-dependent function of RIPK1. This platform requires a non-apoptotic function of caspase-8, but no caspase-3 or caspase-8 cleavage. It may represent a DNA damage-sensing mechanism in hepatocytes that can act via JNK and subsequent phosphorylation of the histone variant H2AX.
%K Fadd protein, mouse (NLM Chemicals)
%K Fas-Associated Death Domain Protein (NLM Chemicals)
%K Histones (NLM Chemicals)
%K Mcl1 protein, mouse (NLM Chemicals)
%K Myeloid Cell Leukemia Sequence 1 Protein (NLM Chemicals)
%K Receptors, Tumor Necrosis Factor, Type I (NLM Chemicals)
%K gamma-H2AX protein, mouse (NLM Chemicals)
%K Receptor-Interacting Protein Serine-Threonine Kinases (NLM Chemicals)
%K Ripk1 protein, mouse (NLM Chemicals)
%K JNK Mitogen-Activated Protein Kinases (NLM Chemicals)
%K Caspase 8 (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:28898696
%2 pmc:PMC5598544
%R 10.1016/j.ccell.2017.08.010
%U https://inrepo02.dkfz.de/record/128312