Kupffer Cell-Derived Tnf Triggers Cholangiocellular Tumorigenesis through JNK due to Chronic Mitochondrial Dysfunction and ROS.

• Yuan D Institute of Virology, Technische Universität München and Helmholtz Zentrum München, 81675 Munich, Germany; Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
• Huang S Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
• Berger E Chair of Nutrition and Immunology, Technische Universität München, Gregor-Mendel-Straße 2, 85350 Freising-Weihenstephan, Germany.
• Liu L Department of Surgery, Technische Universität München, 81675 Munich, Germany.
• Gross N 2nd Department of Internal Medicine, Klinikum Rechts der Isar, Technische Universität München, 81675 Munich, Germany.
• Heinzmann F Department of Internal Medicine VIII, University Hospital Tübingen, 72076 Tübingen, Germany; Department of Physiology I, Institute of Physiology, Eberhard Karls University Tübingen, 72076 Tübingen, Germany.
• Ringelhan M Institute of Virology, Technische Universität München and Helmholtz Zentrum München, 81675 Munich, Germany; 2nd Department of Internal Medicine, Klinikum Rechts der Isar, Technische Universität München, 81675 Munich, Germany.
• Connor TO Institute of Virology, Technische Universität München and Helmholtz Zentrum München, 81675 Munich, Germany; Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
• Stadler M Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
• Meister M Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
• Weber J 2nd Department of Internal Medicine, Klinikum Rechts der Isar, Technische Universität München, 81675 Munich, Germany.
• Öllinger R 2nd Department of Internal Medicine, Klinikum Rechts der Isar, Technische Universität München, 81675 Munich, Germany.
• Simonavicius N Institute of Virology, Technische Universität München and Helmholtz Zentrum München, 81675 Munich, Germany.
• Reisinger F Institute of Virology, Technische Universität München and Helmholtz Zentrum München, 81675 Munich, Germany.
• Hartmann D Department of Surgery, Technische Universität München, 81675 Munich, Germany.
• Meyer R Genome Technology Branch, National Human Genome Research Institute, U.S. National Institutes of Health, Bethesda, MD 20892, USA.
• Reich M Clinic for Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine University, 40204 Düsseldorf, Germany.
• Seehawer M Department of Internal Medicine VIII, University Hospital Tübingen, 72076 Tübingen, Germany; Department of Physiology I, Institute of Physiology, Eberhard Karls University Tübingen, 72076 Tübingen, Germany.
• Leone V Institute of Virology, Technische Universität München and Helmholtz Zentrum München, 81675 Munich, Germany.
• Höchst B Institute of Molecular Immunology, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
• Wohlleber D Institute of Molecular Immunology, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
• Jörs S 2nd Department of Internal Medicine, Klinikum Rechts der Isar, Technische Universität München, 81675 Munich, Germany.
• Prinz M Institute of Neuropathology, University of Freiburg, 79106 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79106 Freiburg, Germany.
• Spalding D Department of Surgery and Cancer, Imperial College London, London SW7 2AZ, UK.
• Protzer U Institute of Virology, Technische Universität München and Helmholtz Zentrum München, 81675 Munich, Germany.
• Luedde T Division of Gastroenterology, Hepatology and Hepatobiliary Oncology, RWTH Aachen University, 52074 Aachen, Germany.
• Terracciano L Institute of Pathology, University Hospital of Basel, 4003 Basel, Switzerland.
• Matter M Institute of Pathology, University Hospital of Basel, 4003 Basel, Switzerland.
• Longerich T Institute of Pathology, University Hospital RWTH, 52074 Aachen, Germany.
• Knolle P Institute of Molecular Immunology, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
• Ried T Genome Technology Branch, National Human Genome Research Institute, U.S. National Institutes of Health, Bethesda, MD 20892, USA.
• Keitel V Clinic for Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine University, 40204 Düsseldorf, Germany.
• Geisler F 2nd Department of Internal Medicine, Klinikum Rechts der Isar, Technische Universität München, 81675 Munich, Germany.
• Unger K Research Unit of Radiation Cytogenetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
• Cinnamon E The Lautenberg Center for Immunology and Cancer Research, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
• Pikarsky E The Lautenberg Center for Immunology and Cancer Research, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel; Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
• Hüser N Department of Surgery, Technische Universität München, 81675 Munich, Germany.
• Davis RJ Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
• Tschaharganeh DF Helmholtz-University Group "Cell Plasticity and Epigenetic Remodeling", German Cancer Research Center (DKFZ) & Institute of Pathology University Hospital, 69120 Heidelberg, Germany.
• Rad R 2nd Department of Internal Medicine, Klinikum Rechts der Isar, Technische Universität München, 81675 Munich, Germany.
• Weber A Department of Pathology and Molecular Pathology, University Zurich and University Hospital Zurich, 8091 Zurich, Switzerland.
• Zender L Department of Internal Medicine VIII, University Hospital Tübingen, 72076 Tübingen, Germany; Department of Physiology I, Institute of Physiology, Eberhard Karls University Tübingen, 72076 Tübingen, Germany; Translational Gastrointestinal Oncology Group within the German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
• Haller D Chair of Nutrition and Immunology, Technische Universität München, Gregor-Mendel-Straße 2, 85350 Freising-Weihenstephan, Germany; ZIEL - Institute for Food & Health, Technische Universität München, 85350 Freising-Weihenstephan, Germany. Electronic address: dirk.haller@tum.de.
• Heikenwalder M Institute of Virology, Technische Universität München and Helmholtz Zentrum München, 81675 Munich, Germany; Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. Electronic address: m.heikenwaelder@dkfz-heidelberg.de.

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JNK

Kupffer cell

Tnf

cholastasis

intrahepatic cholangiocarcinoma

mitochondrial dysfunction

pro-inflammatory niche

reactive oxygen species

unfolded protein response

Animals

Bile Duct Neoplasms

Butylated Hydroxyanisole

Carcinogenesis

Cell Line, Tumor

Cell Proliferation

Cell Transformation, Neoplastic

Cholangiocarcinoma

Humans

Kupffer Cells

Liver

MAP Kinase Signaling System

Mice

Mitochondria

Oxidative Stress

Reactive Oxygen Species

Receptors, Tumor Necrosis Factor

Signal Transduction

Tumor Microenvironment

Tumor Necrosis Factor-alpha