@article{discovery10049372,
           title = {A Dual Role of Caspase-8 in Triggering and Sensing Proliferation-Associated DNA Damage, a Key Determinant of Liver Cancer Development},
            year = {2017},
          number = {3},
         journal = {Cancer Cell},
           pages = {342--359},
            note = {{\copyright} 2017 The Authors. Published by Elsevier Inc. This is an Open Access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).},
       publisher = {CELL PRESS},
          volume = {32},
           month = {September},
            issn = {1535-6108},
        keywords = {liver, hepatocellular carcinoma, DNA damage response, replication stress, apoptosis},
          author = {Boege, Y and Malehmir, M and Healy, ME and Bettermann, K and Lorentzen, A and Vucur, M and Ahuja, AK and B{\"o}hm, F and Mertens, JC and Shimizu, Y and Frick, L and Remouchamps, C and Mutreja, K and K{\"a}hne, T and Sundaravinayagam, D and Wolf, MJ and Rehrauer, H and Koppe, C and Speicher, T and Padrissa-Alt{\'e}s, S and Maire, R and Schattenberg, JRM and Jeong, J-S and Liu, L and Zwirner, S and Boger, R and H{\"u}ser, N and Davis, RJ and M{\"u}llhaupt, B and Moch, H and Schulze-Bergkamen, H and Clavien, P-A and Werner, S and Borsig, L and Luther, SA and Jost, PJ and Weinlich, R and Unger, K and Behrens, A and Hillert, L and Dillon, C and Di Virgilio, M and Wallach, D and Dejardin, E and Zender, L and Naumann, M and Walczak, H and Green, DR and Lopes, M and Lavrik, I and Luedde, T and Heikenwalder, M and Weber, A},
        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.},
             url = {https://doi.org/10.1016/j.ccell.2017.08.010}
}