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Title: The metabolic co-regulator PGC1α suppresses prostate cancer metastasis
Author: 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, Anna
Pandya, Pahini
Lorente, Mar
Martín Martín, Natalia
Sutherland, James David
Sanchez-Mosquera, Pilar
Bozal Basterra, Laura
Zabala Letona, Amaia
Arruabarrena-Aristorena, Amaia
Berenguer, Antoni
Embade, Nieves
Ugalde Olano, Aitziber
Lacasa-Viscasillas, Isabel
Loizaga Iriarte, Ana
Unda Urzaiz, Miguel
Schultz, Nikolaus
Aransay, Ana Maria
Sanz Moreno, Victoria
Barrio, Rosa
Velasco, Guillermo
Pinton, Paolo
Cordon Cardo, Carlos
Locasale, Jason W.
Gomis i Cabré, Roger
Carracedo, Arkaitz
Keywords: Càncer
Issue Date: 23-May-2016
Publisher: Springer
Abstract: 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.
Note: Versió postprint del document publicat a:
It is part of: Nature Cell Biology, 2016, vol. 18, num. 6, p. 645-56
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ISSN: 1465-7392
Appears in Collections:Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))

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