Identification of a tumor-promoter cholesterol metabolite in human breast cancers acting through the glucocorticoid receptor

Proceedings of the National Academy of Sciences of the United States of America
Maud VoisinSandrine Silvente-Poirot

Abstract

Breast cancer (BC) remains the primary cause of death from cancer among women worldwide. Cholesterol-5,6-epoxide (5,6-EC) metabolism is deregulated in BC but the molecular origin of this is unknown. Here, we have identified an oncometabolism downstream of 5,6-EC that promotes BC progression independently of estrogen receptor α expression. We show that cholesterol epoxide hydrolase (ChEH) metabolizes 5,6-EC into cholestane-3β,5α,6β-triol, which is transformed into the oncometabolite 6-oxo-cholestan-3β,5α-diol (OCDO) by 11β-hydroxysteroid-dehydrogenase-type-2 (11βHSD2). 11βHSD2 is known to regulate glucocorticoid metabolism by converting active cortisol into inactive cortisone. ChEH inhibition and 11βHSD2 silencing inhibited OCDO production and tumor growth. Patient BC samples showed significant increased OCDO levels and greater ChEH and 11βHSD2 protein expression compared with normal tissues. The analysis of several human BC mRNA databases indicated that 11βHSD2 and ChEH overexpression correlated with a higher risk of patient death, highlighting that the biosynthetic pathway producing OCDO is of major importance to BC pathology. OCDO stimulates BC cell growth by binding to the glucocorticoid receptor (GR), the nuclear receptor o...Continue Reading

References

Jun 7, 1996·The Journal of Biological Chemistry·U GundimedaR Gopalakrishna
May 21, 1999·Science·D J ParksJ M Lehmann
Aug 19, 2004·The Journal of Pharmacology and Experimental Therapeutics·Melissa K PulferRobert C Murphy
Jun 7, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Rasoul Alikhani-KoupaeiFelix J Frey
Jul 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Philippe de MedinaSandrine Silvente-Poirot
Jul 26, 2011·Oncogene·M GuedjC Theillet
Aug 6, 2011·Breast Cancer Research and Treatment·Myriam VilascoAnne Gompel
May 23, 2012·Biochimie·Marc Poirot, Sandrine Silvente-Poirot
Oct 30, 2012·Current Opinion in Pharmacology·Sandrine Silvente-Poirot, Marc Poirot
Dec 27, 2012·Molecular and Cellular Endocrinology·Dariusz RatmanKarolien De Bosscher
Jan 18, 2013·Database : the Journal of Biological Databases and Curation·Pascal JézéquelMario Campone
Sep 11, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Maxwell N SkorSuzanne D Conzen
Feb 11, 2014·Biochemical and Biophysical Research Communications·Maud VoisinMarc Poirot
Mar 29, 2014·Science·Sandrine Silvente-Poirot, Marc Poirot
Aug 6, 2014·Proceedings of the National Academy of Sciences of the United States of America·Pejman SorooshSiquan Sun
Nov 30, 2014·Molecular and Cellular Endocrinology·Bo HuangJan-Åke Gustafsson
Feb 11, 2015·Steroids·Luigi IulianoWilliam J Griffiths
Feb 24, 2016·Biochemical Pharmacology·Christine R KeenanAlastair G Stewart
Jan 6, 2017·Nature Reviews. Molecular Cell Biology·Emily R WeikumKeith R Yamamoto
Jan 20, 2017·Nature Communications·Giovanni SorrentinoGiannino Del Sal

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Citations

Jan 10, 2018·Hormones & Cancer·Vladimir DjedovicTheodore J Brown
Dec 5, 2017·Nature Communications·Gregory SegalaSandrine Silvente-Poirot
Nov 22, 2018·Nature Reviews. Endocrinology·Daniela F Quail, Andrew J Dannenberg
Feb 13, 2020·Molecular Genetics & Genomic Medicine·Da JiangYing Li
May 16, 2018·Endocrine-related Cancer·Ninu PouloseRebecca E Steele
Apr 3, 2019·Biochemical Society Transactions·William J Griffiths, Yuqin Wang
Oct 13, 2019·Nature Communications·Demin CaiHong-Wu Chen
Jul 23, 2020·British Journal of Pharmacology·Philippe de MedinaMarc Poirot
Jul 23, 2020·Nature Metabolism·Binlu HuangChenqi Xu
Sep 8, 2018·Frontiers in Endocrinology·Shiro HiramitsuMichihisa Umetani
Jun 22, 2019·The Journal of Clinical Endocrinology and Metabolism·Géraldine VitelliusMarc Lombes
Sep 29, 2020·British Journal of Pharmacology·Francesca LuchettiLuigi Iuliano
Sep 29, 2020·British Journal of Pharmacology·Alzbeta Kloudova-SpalenkovaPavel Soucek
Aug 19, 2018·Cancer Research·Sandrine Silvente-PoirotMarc Poirot
Jan 3, 2021·Toxicology and Applied Pharmacology·Silvia G InderbinenAlex Odermatt
Jul 14, 2019·The Journal of Steroid Biochemistry and Molecular Biology·Irundika Hk DiasPablo Martinez-Lage
Nov 8, 2019·Prostaglandins & Other Lipid Mediators·William J Griffiths, Yuqin Wang
Jan 29, 2021·The FEBS Journal·Yuqin WangWilliam J Griffiths
Jan 21, 2019·Molecular and Cellular Endocrinology·Liqian Ma, Erik R Nelson
Apr 20, 2019·The Journal of Steroid Biochemistry and Molecular Biology·Sayyed Hamed Shahoei, Erik R Nelson
Feb 28, 2021·The American Journal of Pathology·Jamie J Bernard, Elizabeth A Wellberg
Apr 23, 2019·Free Radical Biology & Medicine·William J GriffithsYuqin Wang
Sep 16, 2020·Seminars in Cancer Biology·Diego Gómez-CoronadoMaría E Fernández-Suárez
Aug 4, 2019·The Journal of Steroid Biochemistry and Molecular Biology·Marc PoirotUNKNOWN Team Cholesterol metabolism and therapeutic innovations
Aug 16, 2019·The Journal of Steroid Biochemistry and Molecular Biology·Régis SoulèsBen Allal
May 1, 2021·International Journal of Molecular Sciences·Lara Malik NoureddineCoralie Poulard
Apr 6, 2021·British Journal of Pharmacology·Owein Guillemot-Legris, Giulio G Muccioli
Dec 15, 2020·Seminars in Cancer Biology·Joan Font-DíazAnnabel F Valledor
Aug 19, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Yuting MaMinxin Shi
Mar 17, 2020·Current Medicinal Chemistry·Afshin SamadiMassimiliano Peana

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