LXR stimulates a metabolic switch and reveals cholesterol homeostasis as a statin target in Tasmanian devil facial tumor disease
- Author(s)
- Ikonomopoulou, MP; Lopez-Mancheño, Y; Novelle, MG; Martinez-Uña, M; Gangoda, L; Pal, M; Costa-Machado, LF; Fernandez-Marcos, PJ; Ramm, GA; Fernandez-Rojo, MA;
- Details
- Publication Year 2021-03-16,Volume 34,Issue #11,Page 108851
- Journal Title
- Cell Reports
- Abstract
- Devil facial tumor disease (DFTD) and its lack of available therapies are propelling the Tasmanian devil population toward extinction. This study demonstrates that cholesterol homeostasis and carbohydrate energy metabolism sustain the proliferation of DFTD cells in a cell-type-dependent manner. In addition, we show that the liver-X nuclear receptor-β (LXRβ), a major cholesterol cellular sensor, and its natural ligand 24S-hydroxycholesterol promote the proliferation of DFTD cells via a metabolic switch toward aerobic glycolysis. As a proof of concept of the role of cholesterol homeostasis on DFTD proliferation, we show that atorvastatin, an FDA-approved statin-drug subtype used against human cardiovascular diseases that inhibits cholesterol synthesis, shuts down DFTD energy metabolism and prevents tumor growth in an in vivo DFTD-xenograft model. In conclusion, we show that intervention against cholesterol homeostasis and carbohydrate-dependent energy metabolism by atorvastatin constitutes a feasible biochemical treatment against DFTD, which may assist in the conservation of the Tasmanian devil.
- Publisher
- Cell Press
- Keywords
- AKT/mTOR; Dftd; Lxr; atorvastatin; cholesterol; energy metabolism
- Research Division(s)
- Blood Cells And Blood Cancer
- PubMed ID
- 33730574
- Publisher's Version
- https://doi.org/10.1016/j.celrep.2021.108851
- Open Access at Publisher's Site
https://doi.org/10.1016/j.celrep.2021.108851- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2021-03-26 10:28:27
Last Modified: 2021-03-26 10:59:09