Persistent organic pollutants promote aggressiveness in prostate cancer

被引:4
|
作者
Bunay, Julio [1 ,2 ,3 ]
Kossai, Myriam [2 ,4 ]
Damon-Soubeyrant, Christelle [1 ,2 ,3 ]
De Haze, Angelique [1 ,2 ,3 ]
Saru, Jean-Paul [1 ,2 ,3 ]
Trousson, Amalia [1 ,2 ,3 ]
de Joussineau, Cyrille [1 ,2 ,3 ]
Bouchareb, Erwan [1 ,2 ,3 ]
Kocer, Ayhan [1 ,2 ,3 ]
Vialat, Marine [1 ,2 ,3 ]
Dallel, Sarah [1 ,2 ,3 ,5 ]
Degoul, Francoise [1 ,2 ,3 ]
Bost, Frederic [6 ]
Clavel, Stephan [7 ]
Penault-Llorca, Frederique [2 ,4 ]
Valli, Marie-Pierre [8 ]
Guy, Laurent [8 ]
Matthews, Jason [9 ]
Renaud, Yoan [1 ,2 ,3 ]
Ittmann, Michael [10 ,11 ,12 ,13 ]
Jones, Jeffrey [12 ,14 ,15 ]
Morel, Laurent [1 ,2 ,3 ]
Lobaccaro, Jean-Marc [1 ,2 ,3 ]
Baron, Silvere [1 ,2 ,3 ]
机构
[1] Univ Clermont Auvergne, iGReD, CNRS, INSERM U1103,UMR 6293, 28 Pl Henri Dunant,BP38, F-63001 Clermont Ferrand, France
[2] Grp Canc Clermont Auvergne, 28 Pl Henri Dunant,BP38, F-63001 Clermont Ferrand, France
[3] Ctr Rech Nutr Humaine Auvergne, 58 Blvd Montalembert, F-63009 Clermont Ferrand, France
[4] Univ Clermont Auvergne, Ctr Jean Perrin, INSERM, Imagerie Mol & Strategies Theranost U1240, F-63000 Clermont Ferrand, France
[5] Hop Gabriel Montpied, Serv Endocrinol Diabetol & Malad Metab, CHU Clermont Ferrand, F-63003 Clermont Ferrand, France
[6] Univ Cote Azur, Equipe Labellisee Ligue Natl Canc, INSERM U1065, C3M, F-06204 Nice, France
[7] Univ Cote Azur, Inst Pharmacol Mol & Cellulaire IPMC, CNRS, Sophia Antipolis,UMR7275, Valbonne, France
[8] Univ Clermont Auvergne, Serv Urol, CHU Clermont Ferrand, INSERM,UMR1240, Auvergne, France
[9] Univ Oslo, Inst Basic Med Sci, Oslo, Norway
[10] Baylor Coll Med, Dept Mol & Cellular Biol, One Baylor Plaza, Houston, TX 77030 USA
[11] Baylor Coll Med, Ctr Metab & Expt Therapeut, One Baylor Plaza, Houston, TX 77030 USA
[12] Baylor Coll Med, Dan Duncan Comprehens Canc Ctr, One Baylor Plaza, Houston, TX 77030 USA
[13] Baylor Coll Med, Dept Pathol & Immunol, One Baylor Plaza,Michael E DeBakey VAMC Houston, Houston, TX 77030 USA
[14] Baylor Coll Med, Dept Urol, One Baylor Plaza, Houston, TX 77030 USA
[15] Michael E DeBakey VA Med Ctr, Urol Sect, Operat Care Line, Houston, TX 77030 USA
关键词
POLYCHLORINATED-BIPHENYLS; DISRUPTING CHEMICALS; CELL-MIGRATION; MOUSE MODEL; TCDD; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN; METABOLISM; EXPRESSION; EXPOSURE; AHR;
D O I
10.1038/s41388-023-02788-2
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:2854 / 2867
页数:14
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