LSD1-mediated epigenetic reprogramming drives CENPE expression and prostate cancer progression

Yi Liang, Musaddeque Ahmed, Haiyang Guo, Fraser Soares, Junjie T. Hua, Shuai Gao, Catherine Lu, Christine Poon, Wanting Han, Jens Langstein, Muhammad B. Ekram, Brian Li, Elai Davicioni, Mandeep Takhar, Nicholas Erho, R. Jeffrey Karnes, Dianne Chadwick, Theodorus Van Der Kwast, Paul C. Boutros, Cheryl H. ArrowsmithFelix Y. Feng, Anthony M. Joshua, Amina Zoubeidi, Changmeng Cai, Housheng H. He

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Androgen receptor (AR) signaling is a key driver of prostate cancer, and androgen-deprivation therapy (ADT) is a standard treatment for patients with advanced and metastatic disease. However, patients receiving ADT eventually develop incurable castration-resistant prostate cancer (CRPC). Here, we report that the chromatin modifier LSD1, an important regulator of AR transcriptional activity, undergoes epigenetic reprogramming in CRPC. LSD1 reprogramming in this setting activated a subset of cell-cycle genes, including CENPE, a centromere binding protein and mitotic kinesin. CENPE was regulated by the co-binding of LSD1 and AR to its promoter, which was associated with loss of RB1 in CRPC. Notably, genetic deletion or pharmacological inhibition of CENPE significantly decreases tumor growth. Our findings show how LSD1-mediated epigenetic reprogramming drives CRPC, and they offer a mechanistic rationale for its therapeutic targeting in this disease.

Original languageEnglish (US)
Pages (from-to)5479-5490
Number of pages12
JournalCancer research
Volume77
Issue number20
DOIs
StatePublished - Oct 15 2017

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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