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  • Redmer, TorbenUnit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, Vienna, Austria (författare)

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

  • Artikel/kapitelEngelska2024

Förlag, utgivningsår, omfång ...

  • BioMed Central (BMC),2024
  • electronicrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:umu-225946
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-225946URI
  • https://doi.org/10.1186/s12943-024-02022-xDOI

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  • Språk:engelska
  • Sammanfattning på:engelska

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Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • 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 och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • 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 (författare)
  • 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 (författare)
  • 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 (författare)
  • 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 (författare)
  • 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 (författare)
  • Aufinger, AstridDepartment of Pathology, Medical University of Vienna, Vienna, Austria (författare)
  • 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 (författare)
  • 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 (författare)
  • Kodajova, PetraUnit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, Vienna, Austria (författare)
  • Högler, SandraUnit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, Vienna, Austria (författare)
  • Schlederer, MichaelaDepartment of Pathology, Medical University of Vienna, Vienna, Austria (författare)
  • 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 (författare)
  • Oberhuber, MonikaCenter for Biomarker Research in Medicine, CBmed GmbH, Graz, Austria (författare)
  • 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 (författare)
  • 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 (författare)
  • Miranda, SaraInstitute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Vienna, Austria (författare)
  • Tomberger, MartinaCenter for Biomarker Research in Medicine, CBmed GmbH, Graz, Austria (författare)
  • Harbusch, Nora S.Center for Biomarker Research in Medicine, CBmed GmbH, Graz, Austria (författare)
  • 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 (författare)
  • 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 (författare)
  • Moriggl, RichardDepartment of Biosciences and Medical Biology, Cancer Cluster Salzburg, Paris-Lodron University of Salzburg, Salzburg, Austria (författare)
  • Theurillat, Jean-PhilippeInstitute of Oncology Research, Bellinzona and Faculty of Biomedical Sciences, USI, TI, Lugano, Switzerland (författare)
  • Tichy, BorisCEITEC-Central European Institute of Technology, Masaryk University, Brno, Czech Republic (författare)
  • Bystry, VojtechCEITEC-Central European Institute of Technology, Masaryk University, Brno, Czech Republic (författare)
  • Persson, Jenny L.,ProfessorUmeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Department of Biomedical Sciences, Malmö Universitet, Malmö, Sweden(Swepub:umu)jepe0128 (författare)
  • 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 (författare)
  • Aberger, FritzDepartment of Biosciences and Medical Biology, Cancer Cluster Salzburg, Paris-Lodron University of Salzburg, Salzburg, Austria (författare)
  • Strobl, BirgitInstitute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Vienna, Austria (författare)
  • Pospisilova, SarkaCEITEC-Central European Institute of Technology, Masaryk University, Brno, Czech Republic (författare)
  • Merkel, OlafDepartment of Pathology, Medical University of Vienna, Vienna, Austria (författare)
  • Egger, GerdaDepartment of Pathology, Medical University of Vienna, Vienna, Austria (författare)
  • Lagger, SabineUnit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, Vienna, Austria (författare)
  • 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 (författare)
  • 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)

Sammanhörande titlar

  • Ingår i:Molecular Cancer: BioMed Central (BMC)23:11476-4598

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