PMID- 37587334 OWN - NLM STAT- MEDLINE DCOM- 20230918 LR - 20231005 IS - 1476-5594 (Electronic) IS - 0950-9232 (Linking) VI - 42 IP - 38 DP - 2023 Sep TI - Persistent organic pollutants promote aggressiveness in prostate cancer. PG - 2854-2867 LID - 10.1038/s41388-023-02788-2 [doi] AB - Increasing evidence points towards a causal link between exposure to persistent organic pollutants (POPs) with increased incidence and aggressivity of various cancers. Among these POPs, dioxin and PCB-153 are widely found in our environment and represent a significant source of contamination. Dioxin exposure has already been linked to cancer such as non-Hodgkin's lymphoma, but remains to be more extensively investigated in other cancers. Potential implications of dioxin and PCB-153 in prostate cancer progression spurred us to challenge both ex vivo and in vivo models with low doses of these POPs. We found that dioxin or PCB-153 exposure increased hallmarks of growth and metastasis of prostate cancer cells ex vivo and in grafted NOD-SCID mice. Exposure induced histopathological carcinoma-like patterns in the Pten(pc-/-) mice. We identified up-regulation of Acetyl-CoA Acetyltransferase-1 (ACAT1) involved in ketone bodies pathway as a potential target. Mechanistically, genetic inhibition confirmed that ACAT1 mediated dioxin effect on cell migration. Using public prostate cancer datasets, we confirmed the deregulation of ACAT1 and associated gene encoded ketone bodies pathway enzymes such as OXCT1, BDH1 and HMGCL in advanced prostate cancer. To further explore this link between dioxin and ACAT1 deregulation, we analyzed a unique prostate-tumour tissue collection from the USA veterans exposed to agent orange, known to be highly contaminated by dioxin because of industrial production. We found that ACAT1 histoscore is significantly increased in exposed patients. Our studies reveal the implication of dioxin and PCB-153 to induce a prometastatic programme in prostate tumours and identify ACAT1 deregulation as a key event in this process. CI - (c) 2023. The Author(s), under exclusive licence to Springer Nature Limited. FAU - Bunay, Julio AU - Bunay J AD - Universite Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103, 28, place Henri Dunant, BP38, 63001, Clermont-Ferrand, France. AD - Groupe Cancer Clermont Auvergne, 28, place Henri Dunant, BP38, 63001, Clermont-Ferrand, France. AD - Centre de Recherche en Nutrition Humaine d'Auvergne, 58 Boulevard Montalembert, F-63009, Clermont-Ferrand, France. FAU - Kossai, Myriam AU - Kossai M AUID- ORCID: 0000-0002-1968-652X AD - Groupe Cancer Clermont Auvergne, 28, place Henri Dunant, BP38, 63001, Clermont-Ferrand, France. AD - Centre Jean Perrin, Universite Clermont Auvergne, INSERM, U1240 Imagerie Moleculaire et Strategies Theranostiques, F-63000, Clermont Ferrand, France. FAU - Damon-Soubeyrant, Christelle AU - Damon-Soubeyrant C AUID- ORCID: 0009-0002-8126-240X AD - Universite Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103, 28, place Henri Dunant, BP38, 63001, Clermont-Ferrand, France. AD - Groupe Cancer Clermont Auvergne, 28, place Henri Dunant, BP38, 63001, Clermont-Ferrand, France. AD - Centre de Recherche en Nutrition Humaine d'Auvergne, 58 Boulevard Montalembert, F-63009, Clermont-Ferrand, France. FAU - De Haze, Angelique AU - De Haze A AD - Universite Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103, 28, place Henri Dunant, BP38, 63001, Clermont-Ferrand, France. AD - Groupe Cancer Clermont Auvergne, 28, place Henri Dunant, BP38, 63001, Clermont-Ferrand, France. AD - Centre de Recherche en Nutrition Humaine d'Auvergne, 58 Boulevard Montalembert, F-63009, Clermont-Ferrand, France. FAU - Saru, Jean-Paul AU - Saru JP AD - Universite Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103, 28, place Henri Dunant, BP38, 63001, Clermont-Ferrand, France. AD - Groupe Cancer Clermont Auvergne, 28, place Henri Dunant, BP38, 63001, Clermont-Ferrand, France. AD - Centre de Recherche en Nutrition Humaine d'Auvergne, 58 Boulevard Montalembert, F-63009, Clermont-Ferrand, France. FAU - Trousson, Amalia AU - Trousson A AD - Universite Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103, 28, place Henri Dunant, BP38, 63001, Clermont-Ferrand, France. AD - Groupe Cancer Clermont Auvergne, 28, place Henri Dunant, BP38, 63001, Clermont-Ferrand, France. AD - Centre de Recherche en Nutrition Humaine d'Auvergne, 58 Boulevard Montalembert, F-63009, Clermont-Ferrand, France. FAU - de Joussineau, Cyrille AU - de Joussineau C AD - Universite Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103, 28, place Henri Dunant, BP38, 63001, Clermont-Ferrand, France. AD - Groupe Cancer Clermont Auvergne, 28, place Henri Dunant, BP38, 63001, Clermont-Ferrand, France. AD - Centre de Recherche en Nutrition Humaine d'Auvergne, 58 Boulevard Montalembert, F-63009, Clermont-Ferrand, France. FAU - Bouchareb, Erwan AU - Bouchareb E AD - Universite Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103, 28, place Henri Dunant, BP38, 63001, Clermont-Ferrand, France. AD - Groupe Cancer Clermont Auvergne, 28, place Henri Dunant, BP38, 63001, Clermont-Ferrand, France. AD - Centre de Recherche en Nutrition Humaine d'Auvergne, 58 Boulevard Montalembert, F-63009, Clermont-Ferrand, France. FAU - Kocer, Ayhan AU - Kocer A AD - Universite Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103, 28, place Henri Dunant, BP38, 63001, Clermont-Ferrand, France. AD - Groupe Cancer Clermont Auvergne, 28, place Henri Dunant, BP38, 63001, Clermont-Ferrand, France. AD - Centre de Recherche en Nutrition Humaine d'Auvergne, 58 Boulevard Montalembert, F-63009, Clermont-Ferrand, France. FAU - Vialat, Marine AU - Vialat M AUID- ORCID: 0000-0001-7093-1175 AD - Universite Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103, 28, place Henri Dunant, BP38, 63001, Clermont-Ferrand, France. AD - Groupe Cancer Clermont Auvergne, 28, place Henri Dunant, BP38, 63001, Clermont-Ferrand, France. AD - Centre de Recherche en Nutrition Humaine d'Auvergne, 58 Boulevard Montalembert, F-63009, Clermont-Ferrand, France. FAU - Dallel, Sarah AU - Dallel S AD - Universite Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103, 28, place Henri Dunant, BP38, 63001, Clermont-Ferrand, France. AD - Groupe Cancer Clermont Auvergne, 28, place Henri Dunant, BP38, 63001, Clermont-Ferrand, France. AD - Centre de Recherche en Nutrition Humaine d'Auvergne, 58 Boulevard Montalembert, F-63009, Clermont-Ferrand, France. AD - Service d'Endocrinologie, Diabetologie et Maladies Metaboliques, CHU Clermont Ferrand, Hopital Gabriel Montpied, F-63003, Clermont-Ferrand, France. FAU - Degoul, Francoise AU - Degoul F AD - Universite Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103, 28, place Henri Dunant, BP38, 63001, Clermont-Ferrand, France. AD - Groupe Cancer Clermont Auvergne, 28, place Henri Dunant, BP38, 63001, Clermont-Ferrand, France. AD - Centre de Recherche en Nutrition Humaine d'Auvergne, 58 Boulevard Montalembert, F-63009, Clermont-Ferrand, France. FAU - Bost, Frederic AU - Bost F AD - Universite Cote d'Azur, INSERM U1065, C3M, Equipe Labellisee Ligue Nationale contre le Cancer, 2022, F-06204, Nice, France. FAU - Clavel, Stephan AU - Clavel S AUID- ORCID: 0000-0003-0484-3112 AD - Universite Cote d'Azur, Institut de Pharmacologie Moleculaire et Cellulaire (IPMC), CNRS UMR7275, Sophia-Antipolis, Valbonne, France. FAU - Penault-Llorca, Frederique AU - Penault-Llorca F AD - Groupe Cancer Clermont Auvergne, 28, place Henri Dunant, BP38, 63001, Clermont-Ferrand, France. AD - Centre Jean Perrin, Universite Clermont Auvergne, INSERM, U1240 Imagerie Moleculaire et Strategies Theranostiques, F-63000, Clermont Ferrand, France. FAU - Valli, Marie-Pierre AU - Valli MP AD - Service d'Urologie, CHU Clermont-Ferrand, UMR1240 INSERM, Universite Clermont-Auvergne, Clermont Ferrand, France. FAU - Guy, Laurent AU - Guy L AD - Service d'Urologie, CHU Clermont-Ferrand, UMR1240 INSERM, Universite Clermont-Auvergne, Clermont Ferrand, France. FAU - Matthews, Jason AU - Matthews J AD - Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway. FAU - Renaud, Yoan AU - Renaud Y AUID- ORCID: 0000-0002-4036-8315 AD - Universite Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103, 28, place Henri Dunant, BP38, 63001, Clermont-Ferrand, France. AD - Groupe Cancer Clermont Auvergne, 28, place Henri Dunant, BP38, 63001, Clermont-Ferrand, France. AD - Centre de Recherche en Nutrition Humaine d'Auvergne, 58 Boulevard Montalembert, F-63009, Clermont-Ferrand, France. FAU - Ittmann, Michael AU - Ittmann M AUID- ORCID: 0000-0003-4802-0978 AD - Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA. AD - Center for Metabolism and Experimental Therapeutics, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA. AD - Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA. AD - Department of Pathology and Immunology, Baylor College of Medicine, One Baylor Plaza, and Michael E. DeBakey VAMC Houston, Houston, TX, 77030, USA. FAU - Jones, Jeffrey AU - Jones J AD - Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA. AD - Department of Urology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA. AD - Operative Care Line, Urology Section, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, 77030, USA. FAU - Morel, Laurent AU - Morel L AD - Universite Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103, 28, place Henri Dunant, BP38, 63001, Clermont-Ferrand, France. AD - Groupe Cancer Clermont Auvergne, 28, place Henri Dunant, BP38, 63001, Clermont-Ferrand, France. AD - Centre de Recherche en Nutrition Humaine d'Auvergne, 58 Boulevard Montalembert, F-63009, Clermont-Ferrand, France. FAU - Lobaccaro, Jean-Marc AU - Lobaccaro JM AD - Universite Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103, 28, place Henri Dunant, BP38, 63001, Clermont-Ferrand, France. AD - Groupe Cancer Clermont Auvergne, 28, place Henri Dunant, BP38, 63001, Clermont-Ferrand, France. AD - Centre de Recherche en Nutrition Humaine d'Auvergne, 58 Boulevard Montalembert, F-63009, Clermont-Ferrand, France. FAU - Baron, Silvere AU - Baron S AUID- ORCID: 0000-0002-4524-3087 AD - Universite Clermont Auvergne, iGReD, CNRS UMR 6293, INSERM U1103, 28, place Henri Dunant, BP38, 63001, Clermont-Ferrand, France. silvere.baron@uca.fr. AD - Groupe Cancer Clermont Auvergne, 28, place Henri Dunant, BP38, 63001, Clermont-Ferrand, France. silvere.baron@uca.fr. AD - Centre de Recherche en Nutrition Humaine d'Auvergne, 58 Boulevard Montalembert, F-63009, Clermont-Ferrand, France. silvere.baron@uca.fr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230817 PL - England TA - Oncogene JT - Oncogene JID - 8711562 RN - ZRU0C9E32O (2,4,5,2',4',5'-hexachlorobiphenyl) RN - 0 (Persistent Organic Pollutants) RN - 0 (Dioxins) RN - 0 (Polychlorinated Dibenzodioxins) RN - EC 2.3.1.- (Acetyltransferases) SB - IM MH - Male MH - Humans MH - Animals MH - Mice MH - Mice, Inbred NOD MH - Mice, SCID MH - Persistent Organic Pollutants MH - *Dioxins/toxicity MH - *Prostatic Neoplasms/chemically induced/genetics MH - *Polychlorinated Dibenzodioxins MH - Acetyltransferases EDAT- 2023/08/17 00:42 MHDA- 2023/09/18 12:42 CRDT- 2023/08/16 23:33 PHST- 2022/09/15 00:00 [received] PHST- 2023/07/18 00:00 [accepted] PHST- 2023/07/10 00:00 [revised] PHST- 2023/09/18 12:42 [medline] PHST- 2023/08/17 00:42 [pubmed] PHST- 2023/08/16 23:33 [entrez] AID - 10.1038/s41388-023-02788-2 [pii] AID - 10.1038/s41388-023-02788-2 [doi] PST - ppublish SO - Oncogene. 2023 Sep;42(38):2854-2867. doi: 10.1038/s41388-023-02788-2. Epub 2023 Aug 17.