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

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.