CREB5 Promotes Resistance to Androgen-Receptor Antagonists and Androgen Deprivation in Prostate Cancer. Academic Article uri icon

Overview

abstract

  • Androgen-receptor (AR) inhibitors, including enzalutamide, are used for treatment of all metastatic castration-resistant prostate cancers (mCRPCs). However, some patients develop resistance or never respond. We find that the transcription factor CREB5 confers enzalutamide resistance in an open reading frame (ORF) expression screen and in tumor xenografts. CREB5 overexpression is essential for an enzalutamide-resistant patient-derived organoid. In AR-expressing prostate cancer cells, CREB5 interactions enhance AR activity at a subset of promoters and enhancers upon enzalutamide treatment, including MYC and genes involved in the cell cycle. In mCRPC, we found recurrent amplification and overexpression of CREB5. Our observations identify CREB5 as one mechanism that drives resistance to AR antagonists in prostate cancers.

authors

publication date

  • November 19, 2019

Research

keywords

  • Androgen Receptor Antagonists
  • Cyclic AMP Response Element-Binding Protein A

Identity

PubMed Central ID

  • PMC6886683

Scopus Document Identifier

  • 85075126229

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2019.10.068

PubMed ID

  • 31747605

Additional Document Info

volume

  • 29

issue

  • 8