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oai:recercat.cat:2445/1056342025-11-19T19:20:12Zcom_2072_1057col_2072_478908col_2072_478917

00925njm 22002777a 4500 dc Torrano, Verónica author Valcarcel-Jimenez, Lorea author Cortazar, Ana Rosa author Liu, Xiaojing author Urosevic, Jelena author Castillo Martin, Mireia author Fernández Ruiz, Sonia author Morciano, Giampaolo author Caro Maldonado, Alfredo author Guiu, Marc author Zúñiga García, Patricia author Graupera i Garcia-Milà, Mariona author Bellmunt i Tarragó, Anna author Pandya, Pahini author Lorente, Mar author Martín-Martín, Natalia author Sutherland, James David author Sánchez Mosquera, Pilar author Bozal Basterra, Laura author Zabala Letona, Amaia author Arruabarrena-Aristorena, Amaia author Berenguer Llergo, Antoni author Embade, Nieves author Ugalde Olano, Aitziber author Lacasa-Viscasillas, Isabel author Loizaga Iriarte, Ana author Unda Urzaiz, Miguel author Schultz, Nikolaus author Aransay, Ana M. author Sanz Moreno, Victoria author Barrio, Rosa author Velasco, Guillermo author Pinton, Paolo author Cordon Cardo, Carlos author Locasale, Jason W. author Gomis i Cabré, Roger author Carracedo, Arkaitz author 2017-01-16T10:50:26Z 2017-01-16T10:50:26Z 2016-05-23 2017-01-05T09:14:27Z 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. Càncer Metàstasi Cancer Metastasis The metabolic co-regulator PGC1α suppresses prostate cancer metastasis