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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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analyzed JUN expression in clinical prostate cancer samples across different stages and investigated its functional role in a\n                      <jats:italic>Pten<\/jats:italic>\n                      -deficient mouse model. We performed histopathological examinations, transcriptomic analyses and explored the senescence-associated secretory phenotype in the tumor microenvironment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Elevated JUN levels characterized early-stage prostate cancer and predicted improved survival in human and murine samples. Immune-phenotyping of\n                      <jats:italic>Pten<\/jats:italic>\n                      -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-1\u03b2 production.\n                      <jats:italic>Jun<\/jats:italic>\n                      depletion in a\n                      <jats:italic>Pten<\/jats:italic>\n                      -deficient background prevented immune cell attraction which was accompanied by significant reduction of active STAT3 and IL-1\u03b2 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-1\u03b2, TNF-\u03b1, CCL3 and CCL8 in\n                      <jats:italic>Pten<\/jats:italic>\n                      -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\n                      <jats:italic>Pten<\/jats:italic>\n                      -deficient prostates interfered with the senescence-associated immune clearance and accelerated tumor growth.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1186\/s12943-024-02022-x","type":"journal-article","created":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T04:02:10Z","timestamp":1716955330000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["JUN mediates the senescence associated secretory phenotype and immune cell recruitment to prevent prostate cancer 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Patient consent was waived due to the completely anonymized, retrospective nature of the study.All animal studies were reviewed and approved by the Federal Ministry Republic of Austria for Education, Science and Research and conducted according to regulatory standards (BMWFW-66.009\/0144-WF\/II\/3b\/2014 and the amendments BMWFW-66.009\/0063-WF\/V\/3b\/2017, BMWFW-66.009\/0137-WF\/V\/3b\/2019, BMWFW-66.009\/0359-V\/3b\/2019, 2020\u20130.016.881, 2020\u20130.659.052 and 2022\u20130.325.014).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"114"}}