TY  - JOUR
AU  - Boege, Yannick
AU  - Malehmir, Mohsen
AU  - Healy, Marc E
AU  - Bettermann, Kira
AU  - Lorentzen, Anna
AU  - Vucur, Mihael
AU  - Ahuja, Akshay K
AU  - Böhm, Friederike
AU  - Mertens, Joachim C
AU  - Shimizu, Yutaka
AU  - Frick, Lukas
AU  - Remouchamps, Caroline
AU  - Mutreja, Karun
AU  - Kähne, Thilo
AU  - Sundaravinayagam, Devakumar
AU  - Wolf, Monika J
AU  - Rehrauer, Hubert
AU  - Koppe, Christiane
AU  - Speicher, Tobias
AU  - Padrissa-Altés, Susagna
AU  - Maire, Renaud
AU  - Schattenberg, Jörn M
AU  - Jeong, Ju-Seong
AU  - Liu, Lei
AU  - Zwirner, Stefan
AU  - Boger, Regina
AU  - Hüser, Norbert
AU  - Davis, Roger J
AU  - Müllhaupt, Beat
AU  - Moch, Holger
AU  - Schulze-Bergkamen, Henning
AU  - Clavien, Pierre-Alain
AU  - Werner, Sabine
AU  - Borsig, Lubor
AU  - Luther, Sanjiv A
AU  - Jost, Philipp J
AU  - Weinlich, Ricardo
AU  - Unger, Kristian
AU  - Behrens, Axel
AU  - Hillert, Laura
AU  - Dillon, Christopher
AU  - Di Virgilio, Michela
AU  - Wallach, David
AU  - Dejardin, Emmanuel
AU  - Zender, Lars
AU  - Naumann, Michael
AU  - Walczak, Henning
AU  - Green, Douglas R
AU  - Lopes, Massimo
AU  - Lavrik, Inna
AU  - Luedde, Tom
AU  - Heikenwalder, Mathias
AU  - Weber, Achim
TI  - A Dual Role of Caspase-8 in Triggering and Sensing Proliferation-Associated DNA Damage, a Key Determinant of Liver Cancer Development.
JO  - Cancer cell
VL  - 32
IS  - 3
SN  - 1535-6108
CY  - Cambridge, Mass.
PB  - Cell Press
M1  - DKFZ-2017-04329
SP  - 342 - 359.e10
PY  - 2017
AB  - 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.
KW  - Fadd protein, mouse (NLM Chemicals)
KW  - Fas-Associated Death Domain Protein (NLM Chemicals)
KW  - Histones (NLM Chemicals)
KW  - Mcl1 protein, mouse (NLM Chemicals)
KW  - Myeloid Cell Leukemia Sequence 1 Protein (NLM Chemicals)
KW  - Receptors, Tumor Necrosis Factor, Type I (NLM Chemicals)
KW  - gamma-H2AX protein, mouse (NLM Chemicals)
KW  - Receptor-Interacting Protein Serine-Threonine Kinases (NLM Chemicals)
KW  - Ripk1 protein, mouse (NLM Chemicals)
KW  - JNK Mitogen-Activated Protein Kinases (NLM Chemicals)
KW  - Caspase 8 (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:28898696
C2  - pmc:PMC5598544
DO  - DOI:10.1016/j.ccell.2017.08.010
UR  - https://inrepo02.dkfz.de/record/128312
ER  -