Journal
NATURE CELL BIOLOGY
Volume 18, Issue 6, Pages 645-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncb3357
Keywords
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Categories
Funding
- Ramon y Cajal award
- Basque Department of Industry, Tourism and Trade (Etortek) [2012111086, PI2012-03, 277043]
- Movember
- ISCIII [PI10/01484, PI13/00031]
- FERO VIII Fellowship
- European Research Council [336343]
- Spanish Association Against Cancer (AECC)
- MINECO postdoctoral program
- CIG program from the European commission [660191]
- Basque Government of Education
- Italian Association for Cancer Research [AIRC: IG-14442]
- Italian Ministry of Education, University and Research (COFIN) [20129JLHSY_002]
- Italian Ministry of Education, University and Research (FIRB) [RBAP11FXBC_002]
- Italian Ministry of Education, University and Research (Futuro in Ricerca) [RBFR10EGVP_001]
- Italian Ministry of Health
- MINECO [BFU2014-52282-P, BFU2011-25986]
- Basque Government [PI2012/42]
- Cancer Research UK [C33043/A12065]
- Royal Society [RG110591]
- King's Overseas Scholarship
- Spanish Ministry of Economy and Competitiveness/Instituto de Salud Carlos III (MINECO/ISCIII)
- European Regional Development Fund (ERDF/FEDER) [PS09/01401, PI12/02248, PI15/00339]
- Fundacion Mutua Madrilena
- Fundacio la Marato de TV3
- NIH [P01CA087497]
- National Institutes of Health [R00CA168997, R01CA193256, R21CA201963]
- MINECO (Spain) [SAF2014-59950-P]
- Catalan Government [2014-SGR-725]
- European Union [317250]
- Institute of Health Carlos III (ISC III)
- European Regional Development Fund (ERDF) [PIE13/00022]
- Spanish Government (MINECO)
- FEDER [SAF2013-46196]
- Generalitat de Catalunya AGAUR SGR [535]
- ICREA Funding Source: Custom
- Marie Curie Actions (MSCA) [660191] Funding Source: Marie Curie Actions (MSCA)
- Cancer Research UK [12065] Funding Source: researchfish
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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 1 alpha (PGC1 alpha) suppresses prostate cancer progression and metastasis. A metabolic co-regulator data mining analysis unveiled that PGC1 alpha is downregulated in prostate cancer and associated with disease progression. Using genetically engineered mouse models and xenografts, we demonstrated that PGC1 alpha opposes prostate cancer progression and metastasis. Mechanistically, the use of integrative metabolomics and transcriptomics revealed that PGC1 alpha activates an oestrogen-related receptor alpha (ERR alpha)-dependent transcriptional program to elicit a catabolic state and metastasis suppression. Importantly, a signature based on the PGC1 alpha-ERR alpha pathway exhibited prognostic potential in prostate cancer, thus uncovering the relevance of monitoring and manipulating this pathway for prostate cancer stratification and treatment.
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