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JUN mediates the se...
JUN mediates the senescence associated secretory phenotype and immune cell recruitment to prevent prostate cancer progression
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- Redmer, Torben (author)
- Unit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, Vienna, Austria
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- Raigel, Martin (author)
- Unit 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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- Sternberg, Christina (author)
- Unit 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
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- Ziegler, Roman (author)
- Unit 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
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- Probst, Clara (author)
- Unit 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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- Lindner, Desiree (author)
- Unit 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, Astrid (author)
- Department of Pathology, Medical University of Vienna, Vienna, Austria
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- Limberger, Tanja (author)
- Department 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, Karolina (author)
- 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; CEITEC-Central European Institute of Technology, Masaryk University, Brno, Czech Republic
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- Kodajova, Petra (author)
- Unit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, Vienna, Austria
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- Högler, Sandra (author)
- Unit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, Vienna, Austria
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- Schlederer, Michaela (author)
- Department of Pathology, Medical University of Vienna, Vienna, Austria
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- Stoiber, Stefan (author)
- 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; Christian Doppler Laboratory for Applied Metabolomics, Medical University of Vienna, Vienna, Austria
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- Oberhuber, Monika (author)
- Center for Biomarker Research in Medicine, CBmed GmbH, Graz, Austria
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- Bolis, Marco (author)
- Institute 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. (author)
- 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, Sara (author)
- Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Vienna, Austria
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- Tomberger, Martina (author)
- Center for Biomarker Research in Medicine, CBmed GmbH, Graz, Austria
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- Harbusch, Nora S. (author)
- Center for Biomarker Research in Medicine, CBmed GmbH, Graz, Austria
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- Garces de los Fayos Alonso, Ines (author)
- Unit 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, Felix (author)
- Institute 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, Richard (author)
- Department of Biosciences and Medical Biology, Cancer Cluster Salzburg, Paris-Lodron University of Salzburg, Salzburg, Austria
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- Theurillat, Jean-Philippe (author)
- Institute of Oncology Research, Bellinzona and Faculty of Biomedical Sciences, USI, TI, Lugano, Switzerland
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- Tichy, Boris (author)
- CEITEC-Central European Institute of Technology, Masaryk University, Brno, Czech Republic
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- Bystry, Vojtech (author)
- CEITEC-Central European Institute of Technology, Masaryk University, Brno, Czech Republic
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- Persson, Jenny L., Professor (author)
- Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Department of Biomedical Sciences, Malmö Universitet, Malmö, Sweden
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- Mathas, Stephan (author)
- Charité—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, Fritz (author)
- Department of Biosciences and Medical Biology, Cancer Cluster Salzburg, Paris-Lodron University of Salzburg, Salzburg, Austria
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- Strobl, Birgit (author)
- Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Vienna, Austria
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- Pospisilova, Sarka (author)
- CEITEC-Central European Institute of Technology, Masaryk University, Brno, Czech Republic
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- Merkel, Olaf (author)
- Department of Pathology, Medical University of Vienna, Vienna, Austria
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- Egger, Gerda (author)
- Department of Pathology, Medical University of Vienna, Vienna, Austria
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- Lagger, Sabine (author)
- Unit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, Vienna, Austria
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- Kenner, Lukas (author)
- Unit 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
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(creator_code:org_t)
- BioMed Central (BMC), 2024
- 2024
- English.
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In: Molecular Cancer. - : BioMed Central (BMC). - 1476-4598. ; 23:1
- Related links:
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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Abstract
Subject headings
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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.).
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- AP-1 transcription factors
- Immune infiltration
- JUN
- Prostate cancer
- SASP
- Senescence
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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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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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Molecular Cancer
- By the university
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Umeå University