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

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 a...

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Autores: Ikonomopoulou, María, López Mancheño, Yaiza, Garrido Novelle, Marta, Martínez Uña, Maite, Gangoda, Lahiru, Pal Martin, Costa Machado, Luis Filipe, Fernández-Marcos, Pablo, Ramm, Grant, Fernández Rojo, Manuel
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/94539
Acceso en línea:https://hdl.handle.net/20.500.14352/94539
Access Level:acceso abierto
Palabra clave:576
616.831-006.484
DFTD
Cholesterol
Energy metabolism
LXR
AKT/mTOR
Atorvastatin
Biología celular (Biología)
Oncología
2407.04 Citología
3207 Patología
id ES_fdaeb33eafa6da765d589c528cd25b9b
oai_identifier_str oai:docta.ucm.es:20.500.14352/94539
network_acronym_str ES
network_name_str España
repository_id_str
spelling LXR stimulates a metabolic switch and reveals cholesterol homeostasis as a statin target in Tasmanian devil facial tumor diseaseIkonomopoulou, MaríaLópez Mancheño, YaizaGarrido Novelle, MartaMartínez Uña, MaiteGangoda, LahiruPal MartinCosta Machado, Luis FilipeFernández-Marcos, PabloRamm, GrantFernández Rojo, Manuel576616.831-006.484DFTDCholesterolEnergy metabolismLXRAKT/mTORAtorvastatinBiología celular (Biología)Oncología2407.04 Citología3207 PatologíaDevil 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.ElsevierUniversidad Complutense de Madrid20212021-01-0120212021-01-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/94539reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/945392026-06-02T12:44:21Z
dc.title.none.fl_str_mv LXR stimulates a metabolic switch and reveals cholesterol homeostasis as a statin target in Tasmanian devil facial tumor disease
title LXR stimulates a metabolic switch and reveals cholesterol homeostasis as a statin target in Tasmanian devil facial tumor disease
spellingShingle LXR stimulates a metabolic switch and reveals cholesterol homeostasis as a statin target in Tasmanian devil facial tumor disease
Ikonomopoulou, María
576
616.831-006.484
DFTD
Cholesterol
Energy metabolism
LXR
AKT/mTOR
Atorvastatin
Biología celular (Biología)
Oncología
2407.04 Citología
3207 Patología
title_short LXR stimulates a metabolic switch and reveals cholesterol homeostasis as a statin target in Tasmanian devil facial tumor disease
title_full LXR stimulates a metabolic switch and reveals cholesterol homeostasis as a statin target in Tasmanian devil facial tumor disease
title_fullStr LXR stimulates a metabolic switch and reveals cholesterol homeostasis as a statin target in Tasmanian devil facial tumor disease
title_full_unstemmed LXR stimulates a metabolic switch and reveals cholesterol homeostasis as a statin target in Tasmanian devil facial tumor disease
title_sort LXR stimulates a metabolic switch and reveals cholesterol homeostasis as a statin target in Tasmanian devil facial tumor disease
dc.creator.none.fl_str_mv Ikonomopoulou, María
López Mancheño, Yaiza
Garrido Novelle, Marta
Martínez Uña, Maite
Gangoda, Lahiru
Pal Martin
Costa Machado, Luis Filipe
Fernández-Marcos, Pablo
Ramm, Grant
Fernández Rojo, Manuel
author Ikonomopoulou, María
author_facet Ikonomopoulou, María
López Mancheño, Yaiza
Garrido Novelle, Marta
Martínez Uña, Maite
Gangoda, Lahiru
Pal Martin
Costa Machado, Luis Filipe
Fernández-Marcos, Pablo
Ramm, Grant
Fernández Rojo, Manuel
author_role author
author2 López Mancheño, Yaiza
Garrido Novelle, Marta
Martínez Uña, Maite
Gangoda, Lahiru
Pal Martin
Costa Machado, Luis Filipe
Fernández-Marcos, Pablo
Ramm, Grant
Fernández Rojo, Manuel
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 576
616.831-006.484
DFTD
Cholesterol
Energy metabolism
LXR
AKT/mTOR
Atorvastatin
Biología celular (Biología)
Oncología
2407.04 Citología
3207 Patología
topic 576
616.831-006.484
DFTD
Cholesterol
Energy metabolism
LXR
AKT/mTOR
Atorvastatin
Biología celular (Biología)
Oncología
2407.04 Citología
3207 Patología
description 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.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021-01-01
2021
2021-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/94539
url https://hdl.handle.net/20.500.14352/94539
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300724

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