PMID- 28017612 OWN - NLM STAT- MEDLINE DCOM- 20170613 LR - 20220330 IS - 1878-3686 (Electronic) IS - 1535-6108 (Linking) VI - 31 IP - 1 DP - 2017 Jan 9 TI - RIPK1 Suppresses a TRAF2-Dependent Pathway to Liver Cancer. PG - 94-109 LID - S1535-6108(16)30552-9 [pii] LID - 10.1016/j.ccell.2016.11.009 [doi] AB - Receptor-interacting protein kinase 1 (RIPK1) represents an essential signaling node in cell death and inflammation. Ablation of Ripk1 in liver parenchymal cells (LPC) did not cause a spontaneous phenotype, but led to tumor necrosis factor (TNF)-dependent hepatocyte apoptosis and liver injury without affecting inducible nuclear factor kappaB (NF-kappaB) activation. Loss of Ripk1 induced the TNF-dependent proteasomal degradation of the E3-ligase, TNF receptor-associated factor 2 (TRAF2), in a kinase-independent manner, thereby activating caspase-8. Moreover, loss of both Ripk1 and Traf2 in LPC not only resulted in caspase-8 hyperactivation but also impaired NF-kappaB activation, promoting the spontaneous development of hepatocellular carcinoma. In line, low RIPK1 and TRAF2 expression in human HCCs was associated with an unfavorable prognosis, suggesting that RIPK1 collaborates with TRAF2 to inhibit murine and human hepatocarcinogenesis. CI - Copyright (c) 2017 Elsevier Inc. All rights reserved. FAU - Schneider, Anne T AU - Schneider AT AD - Department of Medicine III, RWTH Aachen University, 52074 Aachen, Germany; Division of Gastroenterology, Hepatology and Hepatobiliary Oncology, RWTH Aachen University, 52074 Aachen, Germany. FAU - Gautheron, Jeremie AU - Gautheron J AD - Department of Medicine III, RWTH Aachen University, 52074 Aachen, Germany; Division of Gastroenterology, Hepatology and Hepatobiliary Oncology, RWTH Aachen University, 52074 Aachen, Germany. FAU - Feoktistova, Maria AU - Feoktistova M AD - Department of Dermatology and Allergology, RWTH Aachen University, 52074 Aachen, Germany. FAU - Roderburg, Christoph AU - Roderburg C AD - Department of Medicine III, RWTH Aachen University, 52074 Aachen, Germany. FAU - Loosen, Sven H AU - Loosen SH AD - Department of Medicine III, RWTH Aachen University, 52074 Aachen, Germany. FAU - Roy, Sanchari AU - Roy S AD - Department of Medicine III, RWTH Aachen University, 52074 Aachen, Germany. FAU - Benz, Fabian AU - Benz F AD - Department of Medicine III, RWTH Aachen University, 52074 Aachen, Germany. FAU - Schemmer, Peter AU - Schemmer P AD - Department of Visceral and Transplantation Surgery, University of Heidelberg, 69120 Heidelberg, Germany. FAU - Buchler, Markus W AU - Buchler MW AD - Department of Visceral and Transplantation Surgery, University of Heidelberg, 69120 Heidelberg, Germany. FAU - Nachbur, Ueli AU - Nachbur U AD - Department of Medical Biology, Walter and Eliza Hall Institute of Medical Research and University of Melbourne, Parkville, VIC 3050/3052, Australia. FAU - Neumann, Ulf P AU - Neumann UP AD - Department of Visceral and Transplantation Surgery, RWTH Aachen University, 52074 Aachen, Germany. FAU - Tolba, Rene AU - Tolba R AD - Department of Laboratory Animal Research, RWTH Aachen University, 52074 Aachen, Germany. FAU - Luedde, Mark AU - Luedde M AD - Department of Cardiology, University Hospital, 24105 Kiel, Germany. FAU - Zucman-Rossi, Jessica AU - Zucman-Rossi J AD - INSERM, UMR-1162, Functional Genomic of Solid Tumors, 75010 Paris, France. FAU - Panayotova-Dimitrova, Diana AU - Panayotova-Dimitrova D AD - Department of Dermatology and Allergology, RWTH Aachen University, 52074 Aachen, Germany. FAU - Leverkus, Martin AU - Leverkus M AD - Department of Dermatology and Allergology, RWTH Aachen University, 52074 Aachen, Germany. FAU - Preisinger, Christian AU - Preisinger C AD - Proteomics Facility, IZKF, RWTH Aachen University, 52074 Aachen, Germany. FAU - Tacke, Frank AU - Tacke F AD - Department of Medicine III, RWTH Aachen University, 52074 Aachen, Germany. FAU - Trautwein, Christian AU - Trautwein C AD - Department of Medicine III, RWTH Aachen University, 52074 Aachen, Germany. FAU - Longerich, Thomas AU - Longerich T AD - Department of Pathology, RWTH Aachen University, 52074 Aachen, Germany. FAU - Vucur, Mihael AU - Vucur M AD - Department of Medicine III, RWTH Aachen University, 52074 Aachen, Germany; Division of Gastroenterology, Hepatology and Hepatobiliary Oncology, RWTH Aachen University, 52074 Aachen, Germany. Electronic address: mvucur@ukaachen.de. FAU - Luedde, Tom AU - Luedde T AD - Department of Medicine III, RWTH Aachen University, 52074 Aachen, Germany; Division of Gastroenterology, Hepatology and Hepatobiliary Oncology, RWTH Aachen University, 52074 Aachen, Germany. Electronic address: tluedde@ukaachen.de. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20161222 PL - United States TA - Cancer Cell JT - Cancer cell JID - 101130617 RN - 0 (NF-kappa B) RN - 0 (PSMD2 protein, human) RN - 0 (TNF Receptor-Associated Factor 2) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 2.7.11.1 (RIPK1 protein, human) RN - EC 2.7.11.1 (Receptor-Interacting Protein Serine-Threonine Kinases) RN - EC 3.4.22.- (Caspase 8) RN - EC 3.4.25.1 (Proteasome Endopeptidase Complex) SB - IM CIN - Hepatology. 2017 Sep;66(3):983-985. PMID: 28520112 MH - Animals MH - Caspase 8/metabolism MH - Hepatocytes/physiology MH - Humans MH - Liver Neoplasms/*etiology/prevention & control MH - Male MH - Mice MH - Mice, Inbred C57BL MH - NF-kappa B/physiology MH - Proteasome Endopeptidase Complex/metabolism MH - Receptor-Interacting Protein Serine-Threonine Kinases/*physiology MH - TNF Receptor-Associated Factor 2/*physiology MH - Tumor Necrosis Factor-alpha/pharmacology OTO - NOTNLM OT - HCC OT - NF-kappaB OT - RIP1 OT - RIP3 OT - RIPK3 OT - apoptosis OT - cIAP-1 OT - caspase-8 OT - hepatocarcinogenesis OT - necroptosis EDAT- 2016/12/27 06:00 MHDA- 2017/06/14 06:00 CRDT- 2016/12/27 06:00 PHST- 2016/01/15 00:00 [received] PHST- 2016/10/11 00:00 [revised] PHST- 2016/11/15 00:00 [accepted] PHST- 2016/12/27 06:00 [pubmed] PHST- 2017/06/14 06:00 [medline] PHST- 2016/12/27 06:00 [entrez] AID - S1535-6108(16)30552-9 [pii] AID - 10.1016/j.ccell.2016.11.009 [doi] PST - ppublish SO - Cancer Cell. 2017 Jan 9;31(1):94-109. doi: 10.1016/j.ccell.2016.11.009. Epub 2016 Dec 22.