PGC1α inhibits polyamine synthesis to suppress prostate cancer aggressiveness

Lisa Kaminski, Stephanie Torrino, Maeva Dufies, Zied Djabari, Romain Haider, Francois Rene Roustan, Emilie Jaune, Kathiane Laurent, Nicolas Nottet, Jean Francois Michiels, Maeva Gesson, Stephane Rocchi, Nathalie M. Mazure, Matthieu Durand, Jean Francois Tanti, Damien Ambrosetti, Stephan Clavel, Issam Ben-Sahra, Frederic Bost*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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 (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.

Original languageEnglish (US)
Pages (from-to)3268-3280
Number of pages13
JournalCancer Research
Volume79
Issue number13
DOIs
StatePublished - Jan 1 2019

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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