SMAD4-dependent barrier constrains prostate cancer growth and metastatic progression. Autonomic nerve development contributes to prostate cancer progression. Prostate intraepithelial neoplasia induced by prostate restricted Akt activation: the MPAKT model. Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis. Pten is essential for embryonic development and tumour suppression. The functions and regulation of the PTEN tumour suppressor. Systemic elevation of PTEN induces a tumor-suppressive metabolic state. Pten positively regulates brown adipose function, energy expenditure, and longevity. Oncometabolites: linking altered metabolism with cancer. Cancer metabolism: fatty acid oxidation in the limelight. Evidence for an alternative glycolytic pathway in rapidly proliferating cells. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Extracellular metabolic energetics can promote cancer progression. 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. 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. Using genetically engineered mouse models and xenografts, we demonstrated that PGC1α opposes 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. Here we show that the transcriptional co-activator peroxisome proliferator-activated receptor gamma co-activator 1α (PGC1α) suppresses prostate cancer progression and metastasis. 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. Nature Cell Biology volume 18, pages 645–656 ( 2016) Cite this articleĬellular transformation and cancer progression is accompanied by changes in the metabolic landscape. The metabolic co-regulator PGC1α suppresses prostate cancer metastasis
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