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

Estrogen Receptor (ERa) is a hormone-driven transcription factor, critically involved in driving tumor cell proliferation in the vast majority of breast cancers (BCas). ERa 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 ERa chromatin binding repertoire, we now know that ERa 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 ERa 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 ERa 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 ERa cistrome dynamics may pave the way for better patient diagnostics and the development of novel therapeutic interventions, ultimately improving cancer care and patient outcome.

Automated summary

The estrogen receptor (ERa) plays a critical role in driving tumor cell proliferation in breast cancer, with its chromatin interactions with DNA being highly versatile and influenced by cellular signaling cascades. Understanding the dynamics of the ERa cistrome may lead to improved patient diagnostics and the development of novel therapeutic interventions, ultimately enhancing cancer care and patient outcomes.