The metabolic co-regulator PGC1α suppresses prostate cancer metastasis.

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Torrano, V; Valcarcel-Jimenez, L; Cortazar, AR; 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; Sutherland, JD; 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, AM; Sanz-Moreno, V; Barrio, R; Velasco, G et al.

Published Date

  • June 2016

Published In

Volume / Issue

  • 18 / 6

Start / End Page

  • 645 - 656

PubMed ID

  • 27214280

Electronic International Standard Serial Number (EISSN)

  • 1476-4679

International Standard Serial Number (ISSN)

  • 1465-7392

Digital Object Identifier (DOI)

  • 10.1038/ncb3357

Language

  • eng