Cancer is perhaps the fastest growing
non-communicable disease in the human population worldwide. Although the molecular mechanism of
cancer initiation and progression is known to some extent, however, the majority of pathways responsible for its onset, development and progression are largely unknown. Many members of the
nuclear receptors (NRs) superfamily of transcriptional factors have key roles in
cancer.
Estrogen-related receptor alpha (ERRα) is one of the members of the NR superfamily and studies have linked it with a wide variety of
cancers. In endocrine-related
cancers such as
breast cancer, ERRα regulates a number of target genes directing cell proliferation and growth independent of
estrogen receptor alpha (ERα). Knockdown of ERRα in a number of
cancer tissues and cell lines significantly reduced
tumor growth and
malignancy indicating dependence on ERRα activity. The pro-
angiogenesis factor vascular endothelial growth factor expression has been shown to be regulated by ERRα and has implications in several types of
cancer. The effect of ERRα on
cancers seems to be multipronged via regulation of cell cycle regulators,
osteopontin,
hypoxia inducible factor-1 as well as several energy metabolism genes that are part of glycolysis, TCA cycle, lipogenesis, etc., providing a metabolic twist to
cancer. In this article, the action of ERRα on various types of
cancers including new developments in this field shall be reviewed.