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@ARTICLE{Boege:128312,
author = {Y. Boege and M. Malehmir and M. E. Healy and K. Bettermann
and A. Lorentzen and M. Vucur and A. K. Ahuja and F. Böhm
and J. C. Mertens and Y. Shimizu and L. Frick and C.
Remouchamps and K. Mutreja and T. Kähne and D.
Sundaravinayagam and M. J. Wolf and H. Rehrauer and C. Koppe
and T. Speicher and S. Padrissa-Altés and R. Maire and J.
M. Schattenberg and J.-S. Jeong and L. Liu and S.
Zwirner$^*$ and R. Boger and N. Hüser and R. J. Davis and
B. Müllhaupt and H. Moch and H. Schulze-Bergkamen and P.-A.
Clavien and S. Werner and L. Borsig and S. A. Luther and P.
J. Jost and R. Weinlich and K. Unger and A. Behrens and L.
Hillert and C. Dillon and M. Di Virgilio and D. Wallach and
E. Dejardin and L. Zender$^*$ and M. Naumann and H. Walczak
and D. R. Green and M. Lopes and I. Lavrik and T. Luedde and
M. Heikenwalder$^*$ and A. Weber},
title = {{A} {D}ual {R}ole of {C}aspase-8 in {T}riggering and
{S}ensing {P}roliferation-{A}ssociated {DNA} {D}amage, a
{K}ey {D}eterminant of {L}iver {C}ancer {D}evelopment.},
journal = {Cancer cell},
volume = {32},
number = {3},
issn = {1535-6108},
address = {Cambridge, Mass.},
publisher = {Cell Press},
reportid = {DKFZ-2017-04329},
pages = {342 - 359.e10},
year = {2017},
abstract = {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.},
keywords = {Fadd protein, mouse (NLM Chemicals) / Fas-Associated Death
Domain Protein (NLM Chemicals) / Histones (NLM Chemicals) /
Mcl1 protein, mouse (NLM Chemicals) / Myeloid Cell Leukemia
Sequence 1 Protein (NLM Chemicals) / Receptors, Tumor
Necrosis Factor, Type I (NLM Chemicals) / gamma-H2AX
protein, mouse (NLM Chemicals) / Receptor-Interacting
Protein Serine-Threonine Kinases (NLM Chemicals) / Ripk1
protein, mouse (NLM Chemicals) / JNK Mitogen-Activated
Protein Kinases (NLM Chemicals) / Caspase 8 (NLM Chemicals)},
cin = {V076 / F180 / L801},
ddc = {610},
cid = {I:(DE-He78)V076-20160331 / I:(DE-He78)F180-20160331 /
I:(DE-He78)L801-20160331},
pnm = {319H - Addenda (POF3-319H)},
pid = {G:(DE-HGF)POF3-319H},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:28898696},
pmc = {pmc:PMC5598544},
doi = {10.1016/j.ccell.2017.08.010},
url = {https://inrepo02.dkfz.de/record/128312},
}