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...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2016 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/105634 |
| Acceso en línea: | https://hdl.handle.net/2445/105634 |
| Access Level: | acceso abierto |
| Palabra clave: | Càncer Metàstasi Cancer Metastasis |
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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.Springer2016info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/105634Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió 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:diposit.ub.edu:2445/1056342026-05-27T06:46:51Z |
| 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 |
| 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 |
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(c) Macmillan, 2016 |
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openAccess |
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application/pdf |
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Springer |
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Springer |
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Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona)) reponame:Dipòsit Digital de la UB instname:Universidad de Barcelona |
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Universidad de Barcelona |
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Dipòsit Digital de la UB |
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Dipòsit Digital de la UB |
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1869414201225641984 |
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15,301603 |