eprintid: 10049372 rev_number: 31 eprint_status: archive userid: 608 dir: disk0/10/04/93/72 datestamp: 2018-06-12 16:55:13 lastmod: 2021-09-20 00:34:27 status_changed: 2018-06-12 16:55:13 type: article metadata_visibility: show creators_name: Boege, Y creators_name: Malehmir, M creators_name: Healy, ME creators_name: Bettermann, K creators_name: Lorentzen, A creators_name: Vucur, M creators_name: Ahuja, AK creators_name: Böhm, F creators_name: Mertens, JC creators_name: Shimizu, Y creators_name: Frick, L creators_name: Remouchamps, C creators_name: Mutreja, K creators_name: Kähne, T creators_name: Sundaravinayagam, D creators_name: Wolf, MJ creators_name: Rehrauer, H creators_name: Koppe, C creators_name: Speicher, T creators_name: Padrissa-Altés, S creators_name: Maire, R creators_name: Schattenberg, JRM creators_name: Jeong, J-S creators_name: Liu, L creators_name: Zwirner, S creators_name: Boger, R creators_name: Hüser, N creators_name: Davis, RJ creators_name: Müllhaupt, B creators_name: Moch, H creators_name: Schulze-Bergkamen, H creators_name: Clavien, P-A creators_name: Werner, S creators_name: Borsig, L creators_name: Luther, SA creators_name: Jost, PJ creators_name: Weinlich, R creators_name: Unger, K creators_name: Behrens, A creators_name: Hillert, L creators_name: Dillon, C creators_name: Di Virgilio, M creators_name: Wallach, D creators_name: Dejardin, E creators_name: Zender, L creators_name: Naumann, M creators_name: Walczak, H creators_name: Green, DR creators_name: Lopes, M creators_name: Lavrik, I creators_name: Luedde, T creators_name: Heikenwalder, M creators_name: Weber, A title: A Dual Role of Caspase-8 in Triggering and Sensing Proliferation-Associated DNA Damage, a Key Determinant of Liver Cancer Development ispublished: pub divisions: UCL divisions: B02 divisions: C10 divisions: D19 divisions: G96 divisions: B03 divisions: C01 divisions: J42 keywords: liver, hepatocellular carcinoma, DNA damage response, replication stress, apoptosis note: © 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/). 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. date: 2017-09-11 date_type: published publisher: CELL PRESS official_url: https://doi.org/10.1016/j.ccell.2017.08.010 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green article_type_text: Journal Article verified: verified_manual elements_id: 1423667 doi: 10.1016/j.ccell.2017.08.010 language_elements: English lyricists_name: Shimizu, Yoshiko lyricists_name: Walczak, Henning lyricists_id: YSHIM67 lyricists_id: HWALC98 actors_name: Laslett, David actors_id: DLASL34 actors_role: owner full_text_status: public publication: Cancer Cell volume: 32 number: 3 pagerange: 342-359 pages: 28 issn: 1535-6108 citation: Boege, Y; Malehmir, M; Healy, ME; Bettermann, K; Lorentzen, A; Vucur, M; Ahuja, AK; ... Weber, A; + view all <#> Boege, Y; Malehmir, M; Healy, ME; Bettermann, K; Lorentzen, A; Vucur, M; Ahuja, AK; Böhm, F; Mertens, JC; Shimizu, Y; Frick, L; Remouchamps, C; Mutreja, K; Kähne, T; Sundaravinayagam, D; Wolf, MJ; Rehrauer, H; Koppe, C; Speicher, T; Padrissa-Altés, S; Maire, R; Schattenberg, JRM; Jeong, J-S; Liu, L; Zwirner, S; Boger, R; Hüser, N; Davis, RJ; Müllhaupt, B; Moch, H; Schulze-Bergkamen, H; Clavien, P-A; Werner, S; Borsig, L; Luther, SA; Jost, PJ; Weinlich, R; Unger, K; Behrens, A; Hillert, L; Dillon, C; Di Virgilio, M; Wallach, D; Dejardin, E; Zender, L; Naumann, M; Walczak, H; Green, DR; Lopes, M; Lavrik, I; Luedde, T; Heikenwalder, M; Weber, A; - view fewer <#> (2017) A Dual Role of Caspase-8 in Triggering and Sensing Proliferation-Associated DNA Damage, a Key Determinant of Liver Cancer Development. Cancer Cell , 32 (3) pp. 342-359. 10.1016/j.ccell.2017.08.010 <https://doi.org/10.1016/j.ccell.2017.08.010>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10049372/1/Walczak_A%20Dual%20Role%20of%20Caspase-8%20in%20Triggering%20and%20Sensing%20Proliferation-Associated%20DNA%20Damage%2C%20a%20Key%20Determinant%20of%20Liver%20Cancer%20Development_VoR.pdf