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Sökning: id:"swepub:oai:DiVA.org:umu-225946" > JUN mediates the se...

JUN mediates the senescence associated secretory phenotype and immune cell recruitment to prevent prostate cancer progression

Redmer, Torben (författare)
Unit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, Vienna, Austria
Raigel, Martin (författare)
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
Sternberg, Christina (författare)
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 (författare)
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
Probst, Clara (författare)
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
Lindner, Desiree (författare)
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
Aufinger, Astrid (författare)
Department of Pathology, Medical University of Vienna, Vienna, Austria
Limberger, Tanja (författare)
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
Trachtova, Karolina (författare)
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
Kodajova, Petra (författare)
Unit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, Vienna, Austria
Högler, Sandra (författare)
Unit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, Vienna, Austria
Schlederer, Michaela (författare)
Department of Pathology, Medical University of Vienna, Vienna, Austria
Stoiber, Stefan (författare)
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
Oberhuber, Monika (författare)
Center for Biomarker Research in Medicine, CBmed GmbH, Graz, Austria
Bolis, Marco (författare)
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
Neubauer, Heidi A. (författare)
Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Vienna, Austria; Institute of Medical Biochemistry, University of Veterinary Medicine Vienna, Vienna, Austria
Miranda, Sara (författare)
Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Vienna, Austria
Tomberger, Martina (författare)
Center for Biomarker Research in Medicine, CBmed GmbH, Graz, Austria
Harbusch, Nora S. (författare)
Center for Biomarker Research in Medicine, CBmed GmbH, Graz, Austria
Garces de los Fayos Alonso, Ines (författare)
Unit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, Vienna, Austria; Department of Pathology, Medical University of Vienna, Vienna, Austria
Sternberg, Felix (författare)
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
Moriggl, Richard (författare)
Department of Biosciences and Medical Biology, Cancer Cluster Salzburg, Paris-Lodron University of Salzburg, Salzburg, Austria
Theurillat, Jean-Philippe (författare)
Institute of Oncology Research, Bellinzona and Faculty of Biomedical Sciences, USI, TI, Lugano, Switzerland
Tichy, Boris (författare)
CEITEC-Central European Institute of Technology, Masaryk University, Brno, Czech Republic
Bystry, Vojtech (författare)
CEITEC-Central European Institute of Technology, Masaryk University, Brno, Czech Republic
Persson, Jenny L., Professor (författare)
Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Department of Biomedical Sciences, Malmö Universitet, Malmö, Sweden
Mathas, Stephan (författare)
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
Aberger, Fritz (författare)
Department of Biosciences and Medical Biology, Cancer Cluster Salzburg, Paris-Lodron University of Salzburg, Salzburg, Austria
Strobl, Birgit (författare)
Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Vienna, Austria
Pospisilova, Sarka (författare)
CEITEC-Central European Institute of Technology, Masaryk University, Brno, Czech Republic
Merkel, Olaf (författare)
Department of Pathology, Medical University of Vienna, Vienna, Austria
Egger, Gerda (författare)
Department of Pathology, Medical University of Vienna, Vienna, Austria
Lagger, Sabine (författare)
Unit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, Vienna, Austria
Kenner, Lukas (författare)
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
Engelska.
Ingår i: Molecular Cancer. - : BioMed Central (BMC). - 1476-4598. ; 23:1
Relaterad länk:
https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
https://urn.kb.se/re...
https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • 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.).

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

AP-1 transcription factors
Immune infiltration
JUN
Prostate cancer
SASP
Senescence

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