Nuclear Receptor Coregulators in Hormone-Dependent Cancers.

Abstract

Simple SummaryAltered nuclear receptor signaling is well-established to contribute to a range of hormone-dependent cancers and therefore they are therapeutic targets, for example in breast and prostate cancer. However, nuclear receptor signaling in the cancer, and in response to therapeutic targeting is frequently altered in part by changes to the expression and function of the large numbers of coregulators that modulate sensitivity of the receptor, change their protein-protein interaction and alter the transcriptional consequences. These coregulators perform numerous roles in terms of regulating nuclear receptor responses and the functional diversity of these interactions is an area of emerging insight. Coregulator interactions, functions, and impacts on nuclear receptor signaling across hormone dependent cancers are the topic of this review.Nuclear receptors (NRs) function collectively as a transcriptional signaling network that mediates gene regulatory actions to either maintain cellular homeostasis in response to hormonal, dietary and other environmental factors, or act as orphan receptors with no known ligand. NR complexes are large and interact with multiple protein partners, collectively termed coregulators. Coregulators are essential for regulating NR activity and can dictate whether a target gene is activated or repressed by a variety of mechanisms including the regulation of chromatin accessibility. Altered expression of coregulators contributes to a variety of hormone-dependent cancers including breast and prostate cancers. Therefore, understanding the mechanisms by which coregulators interact with and modulate the activity of NRs provides opportunities to develop better prognostic and diagnostic approaches, as well as novel therapeutic targets. This review aims to gather and summarize recent studies, techniques and bioinformatics methods used to identify distorted NR coregulator interactions that contribute as cancer drivers in hormone-dependent cancers.