TY - JOUR
T1 - PGC1α inhibits polyamine synthesis to suppress prostate cancer aggressiveness
AU - Kaminski, Lisa
AU - Torrino, Stephanie
AU - Dufies, Maeva
AU - Djabari, Zied
AU - Haider, Romain
AU - Roustan, Francois Rene
AU - Jaune, Emilie
AU - Laurent, Kathiane
AU - Nottet, Nicolas
AU - Michiels, Jean Francois
AU - Gesson, Maeva
AU - Rocchi, Stephane
AU - Mazure, Nathalie M.
AU - Durand, Matthieu
AU - Tanti, Jean Francois
AU - Ambrosetti, Damien
AU - Clavel, Stephan
AU - Ben-Sahra, Issam
AU - Bost, Frederic
N1 - Funding Information:
This work has been supported by the French government, through the UCAJEDI Investments in the Future project managed by the National Research Agency (ANR) with the reference number ANR-15-IDEX- 01. L. Kaminski is supported by the French Ministry of Research. S. Torrino has a grant from the Fondation de France. R. Haider and E. Jaune were supported by the foundation ARC and F.-R. Roustan by the CHU of Nice. I. Ben-Sahra is supported by the NIH R00-CA194192 and LAM Foundation grants. F. Bost, N. M. Mazure, and J.F. Tanti are CNRS investigators. Metabolomics services were performed by theMetabolomics Core Facility at Robert H. LurieComprehensive Cancer Center of Northwestern University and the Beth Israel Deaconess Medical Center Mass Spectrometry Facility of Harvard Medical School.
Funding Information:
We thank Charlotte Hinault for carefully reading the manuscript. This work was supported by a grant from the Fondation ARC pour la recherche sur le Cancer, l'Association pour la Recherche sur les Tumeurs de la Prostate (ARTP), ITMO-Cancer. This work has been supported by the French government, through the UCAJEDI Investments in the Future project managed by the National Research Agency (ANR) with the reference number ANR-15-IDEX-01. L. Kaminski is supported by the French Ministry of Research. S. Torrino has a grant from the Fondation de France. R. Haider and E. Jaune were supported by the foundation ARC and F.-R. Roustan by the CHU of Nice. I. Ben-Sahra is supported by the NIH R00-CA194192 and LAM Foundation grants. F. Bost, N. M. Mazure, and J.F. Tanti are CNRS investigators. Metabolomics services were performed by the Metabolomics Core Facility at Robert H. Lurie Comprehensive Cancer Center of Northwestern University and the Beth Israel Deaconess Medical Center Mass Spectrometry Facility of Harvard Medical School.
Publisher Copyright:
© 2019 American Association for Cancer Research Inc.. All rights reserved.
PY - 2019
Y1 - 2019
N2 - 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 modulation of the polyamine biosynthesis pathway. Mechanistically, PGC1α 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 PGC1α/c-MYC/ODC1 axis regulates polyamine biosynthesis and prostate cancer aggressiveness. In conclusion, downregulation of PGC1α renders prostate cancer cells dependent on polyamine to promote metastasis.
AB - 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 modulation of the polyamine biosynthesis pathway. Mechanistically, PGC1α 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 PGC1α/c-MYC/ODC1 axis regulates polyamine biosynthesis and prostate cancer aggressiveness. In conclusion, downregulation of PGC1α renders prostate cancer cells dependent on polyamine to promote metastasis.
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UR - http://www.scopus.com/inward/citedby.url?scp=85068840527&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-18-2043
DO - 10.1158/0008-5472.CAN-18-2043
M3 - Article
C2 - 31064849
AN - SCOPUS:85068840527
SN - 0008-5472
VL - 79
SP - 3268
EP - 3280
JO - Cancer Research
JF - Cancer Research
IS - 13
ER -
