title: There and back again: The journey of the estrogen-related receptors in the cancer realm.
abstract: The identification of two genes encoding polypeptides with structural features common with the estrogen receptor more than a quarter century ago, referred to as the estrogen-related receptors (ERRs), subsequently led to the discovery of several previously unrecognized hormone responsive systems through the application of reverse endocrinology. Paradoxically, the natural ligand(s) associated with members of the ERR subfamily remains to be identified. While initial studies on the mode of action and physiological functions of the ERRs focused on interaction with estrogen signalling in breast cancer, subsequent work showed that the ERRs are ubiquitous master regulators of cellular energy metabolism. This review aims to demonstrate that the ERRs occupy a central node at the interface of cancer and metabolism, and that modulation of their activity may represent a worthwhile strategy to induce metabolic vulnerability in tumors of various origins and thus achieve a more comprehensive response to current therapies.
authors.affiliation: Goodman Cancer Research Centre, McGill University, 1160 Pine Avenue West, Montréal, QC H3A 1A3, Canada.
authors.forename: Ingrid S
authors.initials: IS
authors.lastname: Tam
authors.affiliation: Goodman Cancer Research Centre, McGill University, 1160 Pine Avenue West, Montréal, QC H3A 1A3, Canada; Departments of Biochemistry, Medicine and Oncology, McGill University, Montréal, PQ H3G 1Y6, Canada. Electronic address: vincent.giguere@mcgill.ca.
authors.forename: Vincent
authors.initials: V
authors.lastname: Giguère
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006801:Humans; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D011960:Receptors, Estrogen / Q000378:metabolism*; D020218:Response Elements; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D014408:Biomarkers, Tumor; D004967:Estrogens; D011960:Receptors, Estrogen; D000097983:ERRalpha Estrogen-Related Receptor; C490917:ESRRG protein, human
keywords: Breast cancer; Metabolism; Mitochondria; Nuclear receptor; Warburg effect