Estrogen Receptor on the move: Cistromic plasticity and its implications in breast cancer

Isabel Mayayo-Peralta, Stefan Prekovic, Wilbert Zwart (Corresponding author)

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Estrogen Receptor (ERα) is a hormone-driven transcription factor, critically involved in driving tumor cell proliferation in the vast majority of breast cancers (BCas). ERα binds the genome at cis-regulatory elements, dictating the expression of a large spectrum of responsive genes in 3D genomic space. While initial reports described a rather static ERα chromatin binding repertoire, we now know that ERα DNA interactions are highly versatile, altered in breast tumor development and progression, and deviate between tumors from patients with differential outcome. Multiple cellular signaling cascades are known to impinge on ERα genomic function, changing its cistrome to retarget the receptor to other regions of the genome and reprogram its impact on breast cell biology. This review describes the current state-of-the-art on which factors manipulate the ERα cistrome and how this alters the response to both endogenous and exogenous hormonal stimuli, ultimately impacting BCa cell progression and response to commonly used therapeutic interventions. Novel insights in ERα cistrome dynamics may pave the way for better patient diagnostics and the development of novel therapeutic interventions, ultimately improving cancer care and patient outcome.

Original languageEnglish
Article number100939
Number of pages13
JournalMolecular Aspects of Medicine
Volume78
DOIs
Publication statusPublished - Apr 2021

Keywords

  • Breast cancer
  • Cistromic plasticity
  • ESR1 mutants
  • Estrogen receptor
  • Kinase signaling
  • Steroid hormone receptor crosstalk
  • Transcriptional regulation

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