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The 5,6‐epoxycholesterol metabolic pathway in breast cancer: Emergence of new pharmacological targets

Abstract : Metabolic pathways have emerged as cornerstones in carcinogenic deregulation providing new therapeutic strategies for cancer management. Recently, a new branch of cholesterol metabolism has been discovered involving the biochemical transformation of 5,6-epoxycholesterols (5,6-ECs). The 5,6-ECs are metabolized in breast cancers to the tumour promoter oncosterone whereas, in normal breast tissue, they are metabolized to the tumour suppressor metabolite, dendrogenin A (DDA). Blocking the mitogenic and invasive potential of oncosterone will present new opportunities for breast cancer treatment. The reactivation of DDA biosynthesis, or its use as a drug, represents promising therapeutic approaches such as DDA-deficiency complementation, activation of breast cancer cell re-differentiation and breast cancer chemoprevention. This review presents current knowledge of the 5,6-EC metabolic pathway in breast cancer, focusing on the 5,6-EC metabolic enzymes ChEH and HSD11B2 and on 5,6-EC metabolite targets, the oxysterol receptor (LXRβ) and the glucocorticoid receptor.
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https://www.hal.inserm.fr/inserm-03084636
Contributor : Marc Poirot <>
Submitted on : Monday, December 21, 2020 - 11:42:36 AM
Last modification on : Tuesday, December 29, 2020 - 11:09:26 AM

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Philippe Medina, Khadijetou Diallo, Emilie Huc‐claustre, Mehdi Attia, Régis Soulès, et al.. The 5,6‐epoxycholesterol metabolic pathway in breast cancer: Emergence of new pharmacological targets. British Journal of Pharmacology, Wiley, 2020, Online ahead of print. ⟨10.1111/bph.15205⟩. ⟨inserm-03084636⟩

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