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JUN mediates the se...
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Redmer, TorbenUnit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, Vienna, Austria
(author)
JUN mediates the senescence associated secretory phenotype and immune cell recruitment to prevent prostate cancer progression
- Article/chapterEnglish2024
Publisher, publication year, extent ...
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BioMed Central (BMC),2024
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electronicrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:umu-225946
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-225946URI
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https://doi.org/10.1186/s12943-024-02022-xDOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Background: Prostate cancer develops through malignant transformation of the prostate epithelium in a stepwise, mutation-driven process. Although activator protein-1 transcription factors such as JUN have been implicated as potential oncogenic drivers, the molecular programs contributing to prostate cancer progression are not fully understood.Methods: We analyzed JUN expression in clinical prostate cancer samples across different stages and investigated its functional role in a Pten-deficient mouse model. We performed histopathological examinations, transcriptomic analyses and explored the senescence-associated secretory phenotype in the tumor microenvironment.Results: Elevated JUN levels characterized early-stage prostate cancer and predicted improved survival in human and murine samples. Immune-phenotyping of Pten-deficient prostates revealed high accumulation of tumor-infiltrating leukocytes, particularly innate immune cells, neutrophils and macrophages as well as high levels of STAT3 activation and IL-1β production. Jun depletion in a Pten-deficient background prevented immune cell attraction which was accompanied by significant reduction of active STAT3 and IL-1β and accelerated prostate tumor growth. Comparative transcriptome profiling of prostate epithelial cells revealed a senescence-associated gene signature, upregulation of pro-inflammatory processes involved in immune cell attraction and of chemokines such as IL-1β, TNF-α, CCL3 and CCL8 in Pten-deficient prostates. Strikingly, JUN depletion reversed both the senescence-associated secretory phenotype and senescence-associated immune cell infiltration but had no impact on cell cycle arrest. As a result, JUN depletion in Pten-deficient prostates interfered with the senescence-associated immune clearance and accelerated tumor growth.Conclusions: Our results suggest that JUN acts as tumor-suppressor and decelerates the progression of prostate cancer by transcriptional regulation of senescence- and inflammation-associated genes. This study opens avenues for novel treatment strategies that could impede disease progression and improve patient outcomes. Graphical Abstract: (Figure presented.).
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Raigel, MartinUnit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, Vienna, Austria; Department of Pathology, Medical University of Vienna, Vienna, Austria; Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria
(author)
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Sternberg, ChristinaUnit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, Vienna, Austria; Department of Pathology, Medical University of Vienna, Vienna, Austria; Biochemical Institute, University of Kiel, Kiel, Germany
(author)
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Ziegler, RomanUnit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, Vienna, Austria; Department of Cell Biology, Charles University, Prague, Czech Republic and Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University (BIOCEV), Vestec u Prahy, Czech Republic
(author)
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Probst, ClaraUnit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, Vienna, Austria; Department of Pathology, Medical University of Vienna, Vienna, Austria; Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria
(author)
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Lindner, DesireeUnit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, Vienna, Austria; Department of Pathology, Medical University of Vienna, Vienna, Austria; Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria
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Aufinger, AstridDepartment of Pathology, Medical University of Vienna, Vienna, Austria
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Limberger, TanjaDepartment of Pathology, Medical University of Vienna, Vienna, Austria; Center for Biomarker Research in Medicine (CBmed) Vienna, Core-Lab2, Medical University of Vienna, Vienna, Austria
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Trachtova, KarolinaDepartment of Pathology, Medical University of Vienna, Vienna, Austria; Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria; CEITEC-Central European Institute of Technology, Masaryk University, Brno, Czech Republic
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Kodajova, PetraUnit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, Vienna, Austria
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Högler, SandraUnit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, Vienna, Austria
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Schlederer, MichaelaDepartment of Pathology, Medical University of Vienna, Vienna, Austria
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Stoiber, StefanDepartment of Pathology, Medical University of Vienna, Vienna, Austria; Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Applied Metabolomics, Medical University of Vienna, Vienna, Austria
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Oberhuber, MonikaCenter for Biomarker Research in Medicine, CBmed GmbH, Graz, Austria
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Bolis, MarcoInstitute of Oncology Research, Bellinzona and Faculty of Biomedical Sciences, USI, TI, Lugano, Switzerland; Computational Oncology Unit, Department of Oncology, Istituto di Richerche Farmacologiche ‘Mario Negri’ IRCCS, Milano, Italy; Bioinformatics Core Unit, Swiss Institute of Bioinformatics, TI, Bellinzona, Switzerland
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Neubauer, Heidi A.Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Vienna, Austria; Institute of Medical Biochemistry, University of Veterinary Medicine Vienna, Vienna, Austria
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Miranda, SaraInstitute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Vienna, Austria
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Tomberger, MartinaCenter for Biomarker Research in Medicine, CBmed GmbH, Graz, Austria
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Harbusch, Nora S.Center for Biomarker Research in Medicine, CBmed GmbH, Graz, Austria
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Garces de los Fayos Alonso, InesUnit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, Vienna, Austria; Department of Pathology, Medical University of Vienna, Vienna, Austria
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Sternberg, FelixInstitute of Physiology, Pathophysiology and Biophysics, University of Veterinary Medicine Vienna, Vienna, Austria; Department of Nutritional Sciences, Faculty of Life Sciences, University of Vienna, Vienna, Austria
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Moriggl, RichardDepartment of Biosciences and Medical Biology, Cancer Cluster Salzburg, Paris-Lodron University of Salzburg, Salzburg, Austria
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Theurillat, Jean-PhilippeInstitute of Oncology Research, Bellinzona and Faculty of Biomedical Sciences, USI, TI, Lugano, Switzerland
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Tichy, BorisCEITEC-Central European Institute of Technology, Masaryk University, Brno, Czech Republic
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Bystry, VojtechCEITEC-Central European Institute of Technology, Masaryk University, Brno, Czech Republic
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Persson, Jenny L.,ProfessorUmeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Department of Biomedical Sciences, Malmö Universitet, Malmö, Sweden(Swepub:umu)jepe0128
(author)
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Mathas, StephanCharité—Universitätsmedizin Berlin, Hematology, Oncology and Tumor Immunology, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Group Biology of Malignant Lymphomas, Berlin, Germany; Experimental and Clinical Research Center (ECRC), a cooperation between the MDC and the Charité, Berlin, Germany
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Aberger, FritzDepartment of Biosciences and Medical Biology, Cancer Cluster Salzburg, Paris-Lodron University of Salzburg, Salzburg, Austria
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Strobl, BirgitInstitute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Vienna, Austria
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Pospisilova, SarkaCEITEC-Central European Institute of Technology, Masaryk University, Brno, Czech Republic
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Merkel, OlafDepartment of Pathology, Medical University of Vienna, Vienna, Austria
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Egger, GerdaDepartment of Pathology, Medical University of Vienna, Vienna, Austria
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Lagger, SabineUnit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, Vienna, Austria
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Kenner, LukasUnit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, Vienna, Austria; Department of Pathology, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Applied Metabolomics, Medical University of Vienna, Vienna, Austria; Center for Biomarker Research in Medicine, CBmed GmbH, Graz, Austria; Comprehensive Cancer Center, Medical University Vienna, Vienna, Austria
(author)
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Unit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, Vienna, AustriaUnit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, Vienna, Austria; Department of Pathology, Medical University of Vienna, Vienna, Austria; Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria
(creator_code:org_t)
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In:Molecular Cancer: BioMed Central (BMC)23:11476-4598
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Redmer, Torben
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Raigel, Martin
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Sternberg, Chris ...
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Ziegler, Roman
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Probst, Clara
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Lindner, Desiree
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Aufinger, Astrid
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Limberger, Tanja
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Trachtova, Karol ...
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Kodajova, Petra
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Högler, Sandra
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Schlederer, Mich ...
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Stoiber, Stefan
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Oberhuber, Monik ...
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Bolis, Marco
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Neubauer, Heidi ...
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Miranda, Sara
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Tomberger, Marti ...
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Harbusch, Nora S ...
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Garces de los Fa ...
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Sternberg, Felix
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Moriggl, Richard
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Theurillat, Jean ...
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Tichy, Boris
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Bystry, Vojtech
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Persson, Jenny L ...
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Mathas, Stephan
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Aberger, Fritz
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Strobl, Birgit
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Pospisilova, Sar ...
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Merkel, Olaf
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Egger, Gerda
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Lagger, Sabine
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Kenner, Lukas
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Molecular Cancer
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