Estrogen-related receptor alpha in select host functions and cancer: new frontiers

Abstract

Eukaryotic gene expression is under the tight control of transcription factors, which includes the estrogen-related receptor alpha (ERRα). The endogenous ligand(s) acting as ERRα agonist has not been identified and confirmed. ERRα is a prominent member of the nuclear receptors super-family with major roles in energy metabolism, including immunity, cell growth, proliferation and differentiation and a host of other functions in animals. The actions exerted by ERRα towards gene expression regulation are often in association with other transcriptional factors, receptors and signal mediators. Metabolic regulation by ERRα is known for some time that has tremendous impact on host biology like autophagy, angiogenesis, mitochondrial activity, including lipid metabolism. Cellular metabolism and cancer has intricate relationship. On account of the participation of ERRα in metabolism, it has been implicated in various types of cancer onset and progression. In a number of findings, ERRα has been demonstrated to influence several types of cancers, exhibiting as a negative prognostic marker for many. Such diverse role associated with ERRα is due to its interaction with numerous transcriptional factors and other signalling pathways that culminate in providing optimal gene regulation. These observations points to the crucial regulatory roles of ERRα in health and disease. In this article, some of the new findings on the influence of ERRα in host metabolism and biology including cancer, shall be reviewed that will provide a concise understanding of this receptor.

Keywords: Angiogenesis; Autophagy; Cancer; Estrogen-related receptor alpha; Metabolism; Nuclear receptors.