title: Integration of ERα-PELP1-HER2 signaling by LSD1 (KDM1A/AOF2) offers combinatorial therapeutic opportunities to circumventing hormone resistance in breast cancer.
abstract: 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.
authors.forename: Idriss M
authors.initials: IM
authors.lastname: Bennani-Baiti
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D056970:Co-Repressor Proteins / Q000235:genetics*; D005260:Female; D056466:Histone Demethylases / Q000378:metabolism*; D006801:Humans; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D056970:Co-Repressor Proteins; D014157:Transcription Factors; D056466:Histone Demethylases