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A Dual Role of Caspase-8 in Triggering and Sensing Proliferation-Associated DNA Damage, a Key Determinant of Liver Cancer Development
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-asso...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Cell Press
2017
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5598544/ https://www.ncbi.nlm.nih.gov/pubmed/28898696 http://dx.doi.org/10.1016/j.ccell.2017.08.010 |
| _version_ | 1783263927737516032 |
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| author | Boege, Yannick Malehmir, Mohsen Healy, Marc E. Bettermann, Kira Lorentzen, Anna Vucur, Mihael Ahuja, Akshay K. Böhm, Friederike Mertens, Joachim C. Shimizu, Yutaka Frick, Lukas Remouchamps, Caroline Mutreja, Karun Kähne, Thilo Sundaravinayagam, Devakumar Wolf, Monika J. Rehrauer, Hubert Koppe, Christiane Speicher, Tobias Padrissa-Altés, Susagna Maire, Renaud Schattenberg, Jörn M. Jeong, Ju-Seong Liu, Lei Zwirner, Stefan Boger, Regina Hüser, Norbert Davis, Roger J. Müllhaupt, Beat Moch, Holger Schulze-Bergkamen, Henning Clavien, Pierre-Alain Werner, Sabine Borsig, Lubor Luther, Sanjiv A. Jost, Philipp J. Weinlich, Ricardo Unger, Kristian Behrens, Axel Hillert, Laura Dillon, Christopher Di Virgilio, Michela Wallach, David Dejardin, Emmanuel Zender, Lars Naumann, Michael Walczak, Henning Green, Douglas R. Lopes, Massimo Lavrik, Inna Luedde, Tom Heikenwalder, Mathias Weber, Achim |
| author_facet | Boege, Yannick Malehmir, Mohsen Healy, Marc E. Bettermann, Kira Lorentzen, Anna Vucur, Mihael Ahuja, Akshay K. Böhm, Friederike Mertens, Joachim C. Shimizu, Yutaka Frick, Lukas Remouchamps, Caroline Mutreja, Karun Kähne, Thilo Sundaravinayagam, Devakumar Wolf, Monika J. Rehrauer, Hubert Koppe, Christiane Speicher, Tobias Padrissa-Altés, Susagna Maire, Renaud Schattenberg, Jörn M. Jeong, Ju-Seong Liu, Lei Zwirner, Stefan Boger, Regina Hüser, Norbert Davis, Roger J. Müllhaupt, Beat Moch, Holger Schulze-Bergkamen, Henning Clavien, Pierre-Alain Werner, Sabine Borsig, Lubor Luther, Sanjiv A. Jost, Philipp J. Weinlich, Ricardo Unger, Kristian Behrens, Axel Hillert, Laura Dillon, Christopher Di Virgilio, Michela Wallach, David Dejardin, Emmanuel Zender, Lars Naumann, Michael Walczak, Henning Green, Douglas R. Lopes, Massimo Lavrik, Inna Luedde, Tom Heikenwalder, Mathias Weber, Achim |
| author_sort | Boege, Yannick |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-5598544 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2017 |
| publisher | Cell Press |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-55985442017-09-21 A Dual Role of Caspase-8 in Triggering and Sensing Proliferation-Associated DNA Damage, a Key Determinant of Liver Cancer Development Boege, Yannick Malehmir, Mohsen Healy, Marc E. Bettermann, Kira Lorentzen, Anna Vucur, Mihael Ahuja, Akshay K. Böhm, Friederike Mertens, Joachim C. Shimizu, Yutaka Frick, Lukas Remouchamps, Caroline Mutreja, Karun Kähne, Thilo Sundaravinayagam, Devakumar Wolf, Monika J. Rehrauer, Hubert Koppe, Christiane Speicher, Tobias Padrissa-Altés, Susagna Maire, Renaud Schattenberg, Jörn M. Jeong, Ju-Seong Liu, Lei Zwirner, Stefan Boger, Regina Hüser, Norbert Davis, Roger J. Müllhaupt, Beat Moch, Holger Schulze-Bergkamen, Henning Clavien, Pierre-Alain Werner, Sabine Borsig, Lubor Luther, Sanjiv A. Jost, Philipp J. Weinlich, Ricardo Unger, Kristian Behrens, Axel Hillert, Laura Dillon, Christopher Di Virgilio, Michela Wallach, David Dejardin, Emmanuel Zender, Lars Naumann, Michael Walczak, Henning Green, Douglas R. Lopes, Massimo Lavrik, Inna Luedde, Tom Heikenwalder, Mathias Weber, Achim Cancer Cell Article 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. Cell Press 2017-09-11 /pmc/articles/PMC5598544/ /pubmed/28898696 http://dx.doi.org/10.1016/j.ccell.2017.08.010 Text en © 2017 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| spellingShingle | Article Boege, Yannick Malehmir, Mohsen Healy, Marc E. Bettermann, Kira Lorentzen, Anna Vucur, Mihael Ahuja, Akshay K. Böhm, Friederike Mertens, Joachim C. Shimizu, Yutaka Frick, Lukas Remouchamps, Caroline Mutreja, Karun Kähne, Thilo Sundaravinayagam, Devakumar Wolf, Monika J. Rehrauer, Hubert Koppe, Christiane Speicher, Tobias Padrissa-Altés, Susagna Maire, Renaud Schattenberg, Jörn M. Jeong, Ju-Seong Liu, Lei Zwirner, Stefan Boger, Regina Hüser, Norbert Davis, Roger J. Müllhaupt, Beat Moch, Holger Schulze-Bergkamen, Henning Clavien, Pierre-Alain Werner, Sabine Borsig, Lubor Luther, Sanjiv A. Jost, Philipp J. Weinlich, Ricardo Unger, Kristian Behrens, Axel Hillert, Laura Dillon, Christopher Di Virgilio, Michela Wallach, David Dejardin, Emmanuel Zender, Lars Naumann, Michael Walczak, Henning Green, Douglas R. Lopes, Massimo Lavrik, Inna Luedde, Tom Heikenwalder, Mathias Weber, Achim A Dual Role of Caspase-8 in Triggering and Sensing Proliferation-Associated DNA Damage, a Key Determinant of Liver Cancer Development |
| title | A Dual Role of Caspase-8 in Triggering and Sensing Proliferation-Associated DNA Damage, a Key Determinant of Liver Cancer Development |
| title_full | A Dual Role of Caspase-8 in Triggering and Sensing Proliferation-Associated DNA Damage, a Key Determinant of Liver Cancer Development |
| title_fullStr | A Dual Role of Caspase-8 in Triggering and Sensing Proliferation-Associated DNA Damage, a Key Determinant of Liver Cancer Development |
| title_full_unstemmed | A Dual Role of Caspase-8 in Triggering and Sensing Proliferation-Associated DNA Damage, a Key Determinant of Liver Cancer Development |
| title_short | A Dual Role of Caspase-8 in Triggering and Sensing Proliferation-Associated DNA Damage, a Key Determinant of Liver Cancer Development |
| title_sort | dual role of caspase-8 in triggering and sensing proliferation-associated dna damage, a key determinant of liver cancer development |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5598544/ https://www.ncbi.nlm.nih.gov/pubmed/28898696 http://dx.doi.org/10.1016/j.ccell.2017.08.010 |
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