The metabolic co-regulator PGC1α suppresses prostate cancer metastasis Journal Article
| Authors: | Torrano, V.; Valcarcel-Jimenez, L.; Cortazar, A. R.; Liu, X.; Urosevic, J.; Castillo-Martin, M.; Fernández-Ruiz, S.; Morciano, G.; Caro-Maldonado, A.; Guiu, M.; Zúñiga-García, P.; Graupera, M.; Bellmunt, A.; Pandya, P.; Lorente, M.; Martín-Martín, N.; David Sutherland, J.; Sanchez-Mosquera, P.; Bozal-Basterra, L.; Zabala-Letona, A.; Arruabarrena-Aristorena, A.; Berenguer, A.; Embade, N.; Ugalde-Olano, A.; Lacasa-Viscasillas, I.; Loizaga-Iriarte, A.; Unda-Urzaiz, M.; Schultz, N.; Aransay, A. M.; Sanz-Moreno, V.; Barrio, R.; Velasco, G.; Pinton, P.; Cordon-Cardo, C.; Locasale, J. W.; Gomis, R. R.; Carracedo, A. |
| Article Title: | The metabolic co-regulator PGC1α suppresses prostate cancer metastasis |
| 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. |
| Keywords: | controlled study; human tissue; human cell; nonhuman; mouse; animal tissue; transcription initiation; animal experiment; animal model; tumor xenograft; transcriptomics; prostate cancer; cancer inhibition; prostate epithelium; down regulation; mouse model; metabolomics; metastasis inhibition; peroxisome proliferator activated receptor gamma coactivator 1alpha; data mining; cancer prognosis; human; male; priority journal; article; estrogen related receptor alpha |
| Journal Title: | Nature Cell Biology |
| Volume: | 18 |
| Issue: | 6 |
| ISSN: | 1465-7392 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2016-06-01 |
| Start Page: | 645 |
| End Page: | 656 |
| Language: | English |
| DOI: | 10.1038/ncb3357 |
| PROVIDER: | scopus |
| PMCID: | PMC4884178 |
| PUBMED: | 27214280 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 July 2016 -- Source: Scopus |
