Efficacy of Lysine-Specific Demethylase 1 Inhibition in PCa
Abstract
Lysine specific demethylase 1 (LSD1) has been well-characterized as a transcriptional repressor through demethylation of histone 3 at lysine 4, but it can also act to stimulate the transcriptional activity of several transcription factors including androgen receptor (AR) by unclear mechanisms. The data we have generated show that LSD1 broadly stimulates the transcriptional activity of the AR in prostate cancer (PCa) cells. Moreover, we have identified the transcription factor FOXA1 as a potential substrate for LSD1. These results suggest that FOXA1 demethylation by LSD1 may be important for FOXA1 binding to chromatin and recruitment of AR, and provide new insight into the actions of both LSD1 and FOXA1 that may be relevant in a number of cancers. We further found that short-term treatment with LSD1 inhibitors can markedly suppress PCa growth, while stable knockdown of LSD1 had no clear effect on growth. Further studies are needed to understand how PCa cells adapt to LSD1 inhibition or loss, and to determine whether effective therapies targeting LSD1 can be developed for PCa.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2016
- Accession Number
- AD1019304
Entities
People
- Steven P Balk
Organizations
- Beth Israel Deaconess Medical Center