The metabolic co-regulator PGC1α suppresses prostate cancer metastasis

Torrano, Verónica; Valcarcel-Jimenez, Lorea; Cortazar, Ana Rosa; Liu, Xiaojing; Urosevic, Jelena; Castillo Martin, Mireia; Fernández Ruiz, Sonia; Morciano, Giampaolo; Caro Maldonado, Alfredo; Guiu, Marc; Zúñiga García, Patricia; Graupera i Garcia-Milà, Mariona; Bellmunt i Tarragó, Anna; Pandya, Pahini; Lorente, Mar; Martín-Martín, Natalia; Sutherland, James David; Sánchez Mosquera, Pilar; Bozal Basterra, Laura; Zabala Letona, Amaia; Arruabarrena-Aristorena, Amaia; Berenguer Llergo, Antoni; Embade, Nieves; Ugalde Olano, Aitziber; Lacasa-Viscasillas, Isabel; Loizaga Iriarte, Ana; Unda Urzaiz, Miguel; Schultz, Nikolaus; Aransay, Ana M.; Sanz Moreno, Victoria; Barrio, Rosa; Velasco, Guillermo; Pinton, Paolo; Cordon Cardo, Carlos; Locasale, Jason W.; Gomis i Cabré, Roger; Carracedo, Arkaitz

The metabolic co-regulator PGC1α suppresses prostate cancer metastasis

Cellular transformation and cancer progression is accompanied by changes in the metabolic landscape. Master co-regulators of metabolism orchestrate the modulation of multiple metabolic pathways through transcriptional programs, and hence constitute a probabilistically parsimonious mechanism for gene...

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Detalhes bibliográficos
Autores:	Torrano, Verónica, Valcarcel-Jimenez, Lorea, Cortazar, Ana Rosa, Liu, Xiaojing, Urosevic, Jelena, Castillo Martin, Mireia, Fernández Ruiz, Sonia, Morciano, Giampaolo, Caro Maldonado, Alfredo, Guiu, Marc, Zúñiga García, Patricia, Graupera i Garcia-Milà, Mariona, Bellmunt i Tarragó, Anna, Pandya, Pahini, Lorente, Mar, Martín-Martín, Natalia, Sutherland, James David, Sánchez Mosquera, Pilar, Bozal Basterra, Laura, Zabala Letona, Amaia, Arruabarrena-Aristorena, Amaia, Berenguer Llergo, Antoni, Embade, Nieves, Ugalde Olano, Aitziber, Lacasa-Viscasillas, Isabel, Loizaga Iriarte, Ana, Unda Urzaiz, Miguel, Schultz, Nikolaus, Aransay, Ana M., Sanz Moreno, Victoria, Barrio, Rosa, Velasco, Guillermo, Pinton, Paolo, Cordon Cardo, Carlos, Locasale, Jason W., Gomis i Cabré, Roger, Carracedo, Arkaitz
Formato:	artículo
Estado:	Versión aceptada para publicación
Fecha de publicación:	2016
País:	España
Recursos:	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:	Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:	oai:recercat.cat:2445/105634
Acesso em linha:	https://hdl.handle.net/2445/105634
Access Level:	acceso abierto
Palavra-chave:	Càncer Metàstasi Cancer Metastasis

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spelling	The metabolic co-regulator PGC1α suppresses prostate cancer metastasisTorrano, VerónicaValcarcel-Jimenez, LoreaCortazar, Ana RosaLiu, XiaojingUrosevic, JelenaCastillo Martin, MireiaFernández Ruiz, SoniaMorciano, GiampaoloCaro Maldonado, AlfredoGuiu, MarcZúñiga García, PatriciaGraupera i Garcia-Milà, MarionaBellmunt i Tarragó, AnnaPandya, PahiniLorente, MarMartín-Martín, NataliaSutherland, James DavidSánchez Mosquera, PilarBozal Basterra, LauraZabala Letona, AmaiaArruabarrena-Aristorena, AmaiaBerenguer Llergo, AntoniEmbade, NievesUgalde Olano, AitziberLacasa-Viscasillas, IsabelLoizaga Iriarte, AnaUnda Urzaiz, MiguelSchultz, NikolausAransay, Ana M.Sanz Moreno, VictoriaBarrio, RosaVelasco, GuillermoPinton, PaoloCordon Cardo, CarlosLocasale, Jason W.Gomis i Cabré, RogerCarracedo, ArkaitzCàncerMetàstasiCancerMetastasisCellular transformation and cancer progression is accompanied by changes in the metabolic landscape. Master co-regulators of metabolism orchestrate the modulation of multiple metabolic pathways through transcriptional programs, and hence constitute a probabilistically parsimonious mechanism for general metabolic rewiring. Here we show that the transcriptional co-activator peroxisome proliferator-activated receptor gamma co-activator 1α (PGC1α) suppresses prostate cancer progression and metastasis. A metabolic co-regulator data mining analysis unveiled that PGC1α is downregulated in prostate cancer and associated with disease progression. Using genetically engineered mouse models and xenografts, we demonstrated that PGC1α opposes prostate cancer progression and metastasis. Mechanistically, the use of integrative metabolomics and transcriptomics revealed that PGC1α activates an oestrogen-related receptor alpha (ERRα)-dependent transcriptional program to elicit a catabolic state and metastasis suppression. Importantly, a signature based on the PGC1α–ERRα pathway exhibited prognostic potential in prostate cancer, thus uncovering the relevance of monitoring and manipulating this pathway for prostate cancer stratification and treatment.Springer2017201720162017info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersion32 p.application/pdfapplication/pdfhttps://hdl.handle.net/2445/105634Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésVersió postprint del document publicat a: http://dx.doi.org/10.1038/ncb3357Nature Cell Biology, 2016, vol. 18, num. 6, p. 645-56http://dx.doi.org/10.1038/ncb3357info:eu-repo/grantAgreement/EC/H2020/660191(c) Macmillan, 2016info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1056342026-05-29T05:05:01Z
dc.title.none.fl_str_mv	The metabolic co-regulator PGC1α suppresses prostate cancer metastasis
title	The metabolic co-regulator PGC1α suppresses prostate cancer metastasis
spellingShingle	The metabolic co-regulator PGC1α suppresses prostate cancer metastasis Torrano, Verónica Càncer Metàstasi Cancer Metastasis
title_short	The metabolic co-regulator PGC1α suppresses prostate cancer metastasis
title_full	The metabolic co-regulator PGC1α suppresses prostate cancer metastasis
title_fullStr	The metabolic co-regulator PGC1α suppresses prostate cancer metastasis
title_full_unstemmed	The metabolic co-regulator PGC1α suppresses prostate cancer metastasis
title_sort	The metabolic co-regulator PGC1α suppresses prostate cancer metastasis
dc.creator.none.fl_str_mv	Torrano, Verónica Valcarcel-Jimenez, Lorea Cortazar, Ana Rosa Liu, Xiaojing Urosevic, Jelena Castillo Martin, Mireia Fernández Ruiz, Sonia Morciano, Giampaolo Caro Maldonado, Alfredo Guiu, Marc Zúñiga García, Patricia Graupera i Garcia-Milà, Mariona Bellmunt i Tarragó, Anna Pandya, Pahini Lorente, Mar Martín-Martín, Natalia Sutherland, James David Sánchez Mosquera, Pilar Bozal Basterra, Laura Zabala Letona, Amaia Arruabarrena-Aristorena, Amaia Berenguer Llergo, Antoni Embade, Nieves Ugalde Olano, Aitziber Lacasa-Viscasillas, Isabel Loizaga Iriarte, Ana Unda Urzaiz, Miguel Schultz, Nikolaus Aransay, Ana M. Sanz Moreno, Victoria Barrio, Rosa Velasco, Guillermo Pinton, Paolo Cordon Cardo, Carlos Locasale, Jason W. Gomis i Cabré, Roger Carracedo, Arkaitz
author	Torrano, Verónica
author_facet	Torrano, Verónica Valcarcel-Jimenez, Lorea Cortazar, Ana Rosa Liu, Xiaojing Urosevic, Jelena Castillo Martin, Mireia Fernández Ruiz, Sonia Morciano, Giampaolo Caro Maldonado, Alfredo Guiu, Marc Zúñiga García, Patricia Graupera i Garcia-Milà, Mariona Bellmunt i Tarragó, Anna Pandya, Pahini Lorente, Mar Martín-Martín, Natalia Sutherland, James David Sánchez Mosquera, Pilar Bozal Basterra, Laura Zabala Letona, Amaia Arruabarrena-Aristorena, Amaia Berenguer Llergo, Antoni Embade, Nieves Ugalde Olano, Aitziber Lacasa-Viscasillas, Isabel Loizaga Iriarte, Ana Unda Urzaiz, Miguel Schultz, Nikolaus Aransay, Ana M. Sanz Moreno, Victoria Barrio, Rosa Velasco, Guillermo Pinton, Paolo Cordon Cardo, Carlos Locasale, Jason W. Gomis i Cabré, Roger Carracedo, Arkaitz
author_role	author
author2	Valcarcel-Jimenez, Lorea Cortazar, Ana Rosa Liu, Xiaojing Urosevic, Jelena Castillo Martin, Mireia Fernández Ruiz, Sonia Morciano, Giampaolo Caro Maldonado, Alfredo Guiu, Marc Zúñiga García, Patricia Graupera i Garcia-Milà, Mariona Bellmunt i Tarragó, Anna Pandya, Pahini Lorente, Mar Martín-Martín, Natalia Sutherland, James David Sánchez Mosquera, Pilar Bozal Basterra, Laura Zabala Letona, Amaia Arruabarrena-Aristorena, Amaia Berenguer Llergo, Antoni Embade, Nieves Ugalde Olano, Aitziber Lacasa-Viscasillas, Isabel Loizaga Iriarte, Ana Unda Urzaiz, Miguel Schultz, Nikolaus Aransay, Ana M. Sanz Moreno, Victoria Barrio, Rosa Velasco, Guillermo Pinton, Paolo Cordon Cardo, Carlos Locasale, Jason W. Gomis i Cabré, Roger Carracedo, Arkaitz
author2_role	author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Càncer Metàstasi Cancer Metastasis
topic	Càncer Metàstasi Cancer Metastasis
description	Cellular transformation and cancer progression is accompanied by changes in the metabolic landscape. Master co-regulators of metabolism orchestrate the modulation of multiple metabolic pathways through transcriptional programs, and hence constitute a probabilistically parsimonious mechanism for general metabolic rewiring. Here we show that the transcriptional co-activator peroxisome proliferator-activated receptor gamma co-activator 1α (PGC1α) suppresses prostate cancer progression and metastasis. A metabolic co-regulator data mining analysis unveiled that PGC1α is downregulated in prostate cancer and associated with disease progression. Using genetically engineered mouse models and xenografts, we demonstrated that PGC1α opposes prostate cancer progression and metastasis. Mechanistically, the use of integrative metabolomics and transcriptomics revealed that PGC1α activates an oestrogen-related receptor alpha (ERRα)-dependent transcriptional program to elicit a catabolic state and metastasis suppression. Importantly, a signature based on the PGC1α–ERRα pathway exhibited prognostic potential in prostate cancer, thus uncovering the relevance of monitoring and manipulating this pathway for prostate cancer stratification and treatment.
publishDate	2016
dc.date.none.fl_str_mv	2016 2017 2017 2017
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion
format	article
status_str	acceptedVersion
dc.identifier.none.fl_str_mv	https://hdl.handle.net/2445/105634
url	https://hdl.handle.net/2445/105634
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	Versió postprint del document publicat a: http://dx.doi.org/10.1038/ncb3357 Nature Cell Biology, 2016, vol. 18, num. 6, p. 645-56 http://dx.doi.org/10.1038/ncb3357 info:eu-repo/grantAgreement/EC/H2020/660191
dc.rights.none.fl_str_mv	(c) Macmillan, 2016 info:eu-repo/semantics/openAccess
rights_invalid_str_mv	(c) Macmillan, 2016
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	32 p. application/pdf application/pdf
dc.publisher.none.fl_str_mv	Springer
publisher.none.fl_str_mv	Springer
dc.source.none.fl_str_mv	Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona)) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str	Recercat. Dipósit de la Recerca de Catalunya
collection	Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score	15,812429

The metabolic co-regulator PGC1α suppresses prostate cancer metastasis

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