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

British Journal of Pharmacology
Philippe de MedinaMarc Poirot

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. LINKED ARTICLES: This article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit http://onlinelibrary...Continue Reading

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Citations

Nov 17, 2020·Expert Review of Proteomics·Yuqin WangWilliam J Griffiths
Jan 14, 2021·International Journal of Molecular Sciences·Hsing-Ju Wu, Pei-Yi Chu
Jan 29, 2021·The FEBS Journal·Yuqin WangWilliam J Griffiths
Jul 20, 2021·British Journal of Pharmacology·Mark Nixon, Ruth Andrew
Sep 29, 2020·British Journal of Pharmacology·Alzbeta Kloudova-SpalenkovaPavel Soucek

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