Format

Send to

Choose Destination
Cancer Res. 2019 May 7. pii: canres.2043.2018. doi: 10.1158/0008-5472.CAN-18-2043. [Epub ahead of print]

PGC-1α inhibits polyamine synthesis to suppress prostate cancer aggressiveness.

Author information

1
C3M, INSERM U1065.
2
Biomedical department, Centre Scientifique de Monaco.
3
Biochemistry and Molecular Genetics, Northwestern University.
4
Urology, CHU Nice.
5
C3M, INSERM U895.
6
Department of Pathology, CHU Nice, Université de Nice-Sophia Antipolis.
7
U1065, team 1, INSERM.
8
INSERM U1065, C3M, University of Côte d'Azur (UCA).
9
Centre Hospitalier Universitaire de Nice.
10
Department of Pathology, Pasteur Hospital.
11
Department of Biochemistry and Molecular Genetics, Northwestern University.
12
INSERM U1065, C3M, University of Côte d'Azur (UCA) Frederic.Bost@unice.fr.

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 co-activator peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) plays a pleiotropic role in the control of cancer cell metabolism and has been associated with a good prognosis in prostate cancer (PCa). Here we show that PGC-1α represses the metastatic properties of PCa cells via modulation of the polyamine biosynthesis pathway. Mechanistically, PGC-1α 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 prostate cancer patients support the proposition that the PGC-1α/c-MYC/ODC1 axis regulates polyamine biosynthesis and prostate cancer aggressiveness. In conclusion, downregulation of PGC-1α renders PCa cells dependent on polyamine to promote metastasis.

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center