Dataset Information

PGC1? Inhibits Polyamine Synthesis to Suppress Prostate Cancer Aggressiveness.

ABSTRACT: Although tumorigenesis is dependent on the reprogramming of cellular metabolism, the metabolic pathways engaged in the formation of metastases remain largely unknown. The transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1?) plays a pleiotropic role in the control of cancer cell metabolism and has been associated with a good prognosis in prostate cancer. Here, we show that PGC1? represses the metastatic properties of prostate cancer cells via modulation of the polyamine biosynthesis pathway. Mechanistically, PGC1? inhibits the expression of c-MYC and ornithine decarboxylase 1 (ODC1), the rate-limiting enzyme for polyamine synthesis. Analysis of in vivo metastases and clinical data from patients with prostate cancer support the proposition that the PGC1?/c-MYC/ODC1 axis regulates polyamine biosynthesis and prostate cancer aggressiveness. In conclusion, downregulation of PGC1? renders prostate cancer cells dependent on polyamine to promote metastasis. SIGNIFICANCE: These findings show that a major regulator of mitochondrial metabolism controls polyamine synthesis and prostate cancer aggressiveness, with potential applications in therapy and identification of new biomarkers.

SUBMITTER: Kaminski L

PROVIDER: S-EPMC7293888 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

PGC1α Inhibits Polyamine Synthesis to Suppress Prostate Cancer Aggressiveness.

Kaminski Lisa L Torrino Stéphanie S Dufies Maeva M Djabari Zied Z Haider Romain R Roustan François-René FR Jaune Emilie E Laurent Kathiane K Nottet Nicolas N Michiels Jean-François JF Gesson Maeva M Rocchi Stéphane S Mazure Nathalie M NM Durand Matthieu M Tanti Jean-François JF Ambrosetti Damien D Clavel Stephan S Ben-Sahra Issam I Bost Frédéric F

Cancer research 20190507 13

Although tumorigenesis is dependent on the reprogramming of cellular metabolism, the metabolic pathways engaged in the formation of metastases remain largely unknown. The transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) plays a pleiotropic role in the control of cancer cell metabolism and has been associated with a good prognosis in prostate cancer. Here, we show that PGC1α represses the metastatic properties of prostate cancer cells via mo ...[more]

PMID: 31064849

Similar Datasets

Project description:Novel biomarkers for prostate cancer (PCa) diagnosis and prognosis are necessary to improve the accuracy of current ones employed in clinic. We performed a retrospective study between the association of several polymorphisms in the main genes involved in the synthesis and metabolism of sex hormones and PCa risk and aggressiveness. A total of 311 Caucasian men (155 controls and 156 patients) were genotyped for 9 SNPs in AR, CYP17A1, LHCGR, ESR1 and ESR2 genes. Diagnostic PSA serum levels, Gleason score, tumor stage, D´Amico risk and data of clinical progression were obtained for patients at the moment of the diagnosis and after 54 months of follow-up. Chi-squared test were used for comparisons between clinical variables groups, logistic regression for clinical variables associations between SNPs; and Kaplan-Meier for the association between SNPs and time to biochemical progression. We found 5 variants (CYP17A1) rs743572, rs6162, rs6163; (LHCGR) rs2293275 and (ESR2) rs1256049 that were statistically significant according to clinical variables (PSA, D´Amico risk and T stage) on a case-case analysis. Moreover, the presence of A and G alleles in rs743572 and rs6162 respectively, increase the risk of higher PSA levels (>10 ng/?l). With respect to D´Amico risk rs743572 (AG-GG), rs6162 (AG-AA) and rs6163 (AC-AA) were associated with an increased risk; and last, AC and AA genotypes for rs6163 were associated with a shorter biochemical recurrence free survival (BRFS) in patients with radical prostatectomy. In multigene analysis, several variants in SNPs rs2293275, rs6152, rs1062577, rs6162, rs6163, rs1256049 and rs1004467 were described to be associated with a more aggressiveness in patients. However, none of the selected SNPs show significant values between patients and controls. In conclusion, this study identified inherited variants in genes CYP17A1, LHCGR and ESR2 related to more aggressiveness and/or a poor progression of the disease. According to this study, new promise PCa biomarkers for clinical management could be included in these previous SNPs.

Dataset Information

PGC1? Inhibits Polyamine Synthesis to Suppress Prostate Cancer Aggressiveness.

Publications

PGC1α Inhibits Polyamine Synthesis to Suppress Prostate Cancer Aggressiveness.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure