biostudies-literatureBaek AENIDDK NIH HHSNCI NIH HHS864https://www.ebi.ac.uk/biostudies/studies/S-EPMC5636879biostudies-literatureUnknown8(1)Obesity and elevated circulating cholesterol are risk factors for breast cancer recurrence, while the use of statins, cholesterol biosynthesis inhibitors widely used for treating hypercholesterolemia, is associated with improved disease-free survival. Here, we show that cholesterol mediates the metastatic effects of a high-fat diet via its oxysterol metabolite, 27-hydroxycholesterol. Ablation or inhibition of CYP27A1, the enzyme responsible for the rate-limiting step in 27-hydroxycholesterol biosynthesis, significantly reduces metastasis in relevant animal models of cancer. The robust effects of 27-hydroxycholesterol on metastasis requires myeloid immune cell function, and it was found that this oxysterol increases the number of polymorphonuclear-neutrophils and γδ-T cells at distal metastNature communicationsThe cholesterol metabolite 27 hydroxycholesterol facilitates breast cancer metastasis through its actions on immune cells.PMC5636879R01 DK095842R01 DK048807R00 CA172357R01 DK062777Kwon SSullivan PMMcDowell HBThompson JWGunn MDNelson ERMcDonnell DPHe SPillai RVDubois LGYu YAChang CYKemper JKWardell SEBaek AEfalseThe cholesterol metabolite 27 hydroxycholesterol facilitates breast cancer metastasis through its actions on immune cells.Obesity and elevated circulating cholesterol are risk factors for breast cancer recurrence, while the use of statins, cholesterol biosynthesis inhibitors widely used for treating hypercholesterolemia, is associated with improved disease-free survival. Here, we show that cholesterol mediates the metastatic effects of a high-fat diet via its oxysterol metabolite, 27-hydroxycholesterol. Ablation or inhibition of CYP27A1, the enzyme responsible for the rate-limiting step in 27-hydroxycholesterol biosynthesis, significantly reduces metastasis in relevant animal models of cancer. The robust effects of 27-hydroxycholesterol on metastasis requires myeloid immune cell function, and it was found that this oxysterol increases the number of polymorphonuclear-neutrophils and γδ-T cells at distal metast2017-01-01T00:00:00Z2017 Oct2026-05-06T00:03:00.154Z2019-03-27T02:58:42ZS-EPMC56368792902152210.1038/s41467-017-00910-z