Oestrogen-related receptors in breast cancer: control of cellular metabolism and beyond

Oestrogen-related receptors (ERRs) are orphan nuclear receptors that were initially investigated in breast cancer because of their structural relationship to oestrogen receptors. Recent data have shown that the ERRs control vast gene networks that are involved in glycolysis, glutaminolysis, oxidative phosphorylation, nutrient sensing and biosynthesis pathways. In the context of breast cancer, the ERRs affect cellular metabolism in a manner that promotes a Warburg-like phenotype. The ERRs also modulate breast cancer cell metabolism, growth and proliferation through the regulation of key oncoproteins. We discuss the value but also the implications of the complexity of targeting the ERRs for the development of cancer therapeutics.