LXR stimulates a metabolic switch and reveals cholesterol homeostasis as a statin target in Tasmanian devil facial tumor disease.

Autor:	Ikonomopoulou MP; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; The University of Queensland, Brisbane, QLD, Australia; Translational Venomics Laboratory, Madrid Institute for Advanced Studies (IMDEA) Food, Madrid 28049, Spain. Electronic address: maria.ikonomopoulou@imdea.org., Lopez-Mancheño Y; Hepatic Regenerative Medicine Laboratory, Madrid Institute for Advanced Studies (IMDEA) Food, Madrid 28049, Spain., Novelle MG; Hepatic Regenerative Medicine Laboratory, Madrid Institute for Advanced Studies (IMDEA) Food, Madrid 28049, Spain., Martinez-Uña M; Hepatic Regenerative Medicine Laboratory, Madrid Institute for Advanced Studies (IMDEA) Food, Madrid 28049, Spain., Gangoda L; Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Melbourne, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Melbourne, VIC 3052, Australia., Pal M; Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Melbourne, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Melbourne, VIC 3052, Australia., Costa-Machado LF; Metabolic Syndrome Laboratory, Madrid Institute for Advanced Studies (IMDEA) Food, Madrid 28049, Spain., Fernandez-Marcos PJ; Metabolic Syndrome Laboratory, Madrid Institute for Advanced Studies (IMDEA) Food, Madrid 28049, Spain., Ramm GA; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; The University of Queensland, Brisbane, QLD, Australia., Fernandez-Rojo MA; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; The University of Queensland, Brisbane, QLD, Australia; Hepatic Regenerative Medicine Laboratory, Madrid Institute for Advanced Studies (IMDEA) Food, Madrid 28049, Spain. Electronic address: manuel.fernandez@imdea.org.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2021 Mar 16; Vol. 34 (11), pp. 108851.
DOI:	10.1016/j.celrep.2021.108851
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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