Integration of ERα-PELP1-HER2 signaling by LSD1 (KDM1A/AOF2) offers combinatorial therapeutic opportunities to circumventing hormone resistance in breast cancer

Breast Cancer Res. 2012 Sep 17;14(5):112. doi: 10.1186/bcr3249.


LSD1, an epigenetic modifier, and PELP1, an estrogen receptor co-activator, integrate estrogen receptor ERα and HER2 receptor tyrosine kinase signaling to promote aromatase expression and hormone resistance in a preclinical model of post-menopausal breast cancer. In the previous issue of Breast Cancer Research, Cortez et al. show, for the first time, that knockdown or drug-mediated inhibition of PELP1 or LSD1 suppresses LSD1-mediated transcriptionally activating histone marks at ERα target genes, inhibits aromatase gene expression, and sensitizes hormone refractory breast cancer cells to tamoxifen or letrozole treatments. The relevance of PELP1-LSD1 signaling to other nuclear hormone receptor-dependent cancers and structural considerations for the selective drug targeting of LSD1 are further discussed in this editorial.

Publication types

  • Editorial
  • Comment

MeSH terms

  • Animals
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism*
  • Co-Repressor Proteins / genetics*
  • Female
  • Histone Demethylases / metabolism*
  • Humans
  • Transcription Factors / genetics*


  • Co-Repressor Proteins
  • Transcription Factors
  • Histone Demethylases