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http://hdl.handle.net/2445/105634
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 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 |
Keywords: | Càncer Metàstasi Cancer Metastasis |
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: http://dx.doi.org/10.1038/ncb3357 |
It is part of: | Nature Cell Biology, 2016, vol. 18, num. 6, p. 645-56 |
URI: | http://hdl.handle.net/2445/105634 |
Related resource: | http://dx.doi.org/10.1038/ncb3357 |
ISSN: | 1465-7392 |
Appears in Collections: | Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona)) |
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