ERRα protein is stabilized by LSD1 in a demethylation-independent manner

PLoS One. 2017 Nov 30;12(11):e0188871. doi: 10.1371/journal.pone.0188871. eCollection 2017.

Abstract

The LSD1 histone demethylase is highly expressed in breast tumors where it constitutes a factor of poor prognosis and promotes traits of cancer aggressiveness such as cell invasiveness. Recent work has shown that the Estrogen-Related Receptor α (ERRα) induces LSD1 to demethylate the Lys 9 of histone H3. This results in the transcriptional activation of a number of common target genes, several of which being involved in cellular invasion. High expression of ERRα protein is also a factor of poor prognosis in breast tumors. Here we show that, independently of its demethylase activities, LSD1 protects ERRα from ubiquitination, resulting in overexpression of the latter protein. Our data also suggests that the elevation of LSD1 mRNA and protein in breast cancer (as compared to normal tissue) may be a key event to increase ERRα protein, independently of its corresponding mRNA.

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Demethylation
  • ERRalpha Estrogen-Related Receptor
  • Female
  • Histone Demethylases / genetics
  • Histone Demethylases / metabolism*
  • Humans
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism*

Substances

  • Receptors, Estrogen
  • Histone Demethylases
  • KDM1A protein, human

Grants and funding

This work was funded by Ligue contre le Cancer (comité Rhône). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.