RT Journal Article
T1 LXR stimulates a metabolic switch and reveals cholesterol homeostasis as a statin target in Tasmanian devil facial tumor disease
A1 Ikonomopoulou, María
A1 López Mancheño, Yaiza
A1 Garrido Novelle, Marta
A1 Martínez Uña, Maite
A1 Gangoda, Lahiru
A1 Pal Martin, 
A1 Costa Machado, Luis Filipe
A1 Fernández-Marcos, Pablo
A1 Ramm, Grant
A1 Fernández Rojo, Manuel
AB 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.
PB Elsevier
SN 2211-1247
YR 2021
FD 2021
LK https://hdl.handle.net/20.500.14352/94539
UL https://hdl.handle.net/20.500.14352/94539
LA eng
NO Ikonomopoulou, Maria P., et al. «LXR Stimulates a Metabolic Switch and Reveals Cholesterol Homeostasis as a Statin Target in Tasmanian Devil Facial Tumor Disease». Cell Reports, vol. 34, n.o 11, marzo de 2021, p. 108851.  https://doi.org/10.1016/j.celrep.2021.108851.
NO DFTD and FIB cell lines were obtained from the Department of Primary Industries, Parks, Water and Environment (DPIPWE) in Tasmania. The cell lines were established as part of a management plan and adhered to a standard operating practice. We thank Prof. Rajiv Khanna for allowing us to access his fluorescence-activated cell sorting (FACS) facilities at QIMR Berghofer MRI. We thank also Associate Professor Marco Herold from the Walter and Eliza Hall Institute of Medical Research for assisting and providing the facilities of his laboratory to attempt to develop CRISPR-Cas9 AKT1, AKT3, and LXRβ knockout DFTD cells. M.P.I. has been supported by the AMAROUT Marie Curie program (291803-AMAROUT II) and the TALENTO Program of the Regional Madrid Government (2018-T1/BIO-11262); G.A.R. is supported by the National Health and Medical Research Council of Australia (NHMRC) (APP1064533) and the NHMRC Senior Research Fellowship (APP1061332); and M.A.F.-R. is supported by the TALENTO Program of the Regional Madrid Government (2016/T1-BIO-1854).
NO National Health and Medical Research Council of Australia
NO European Commission
NO Comunidad de Madrid
DS Docta Complutense
RD 8 jun 2025