Estrogen-Related Receptor Gamma (ERRγ) as Biomarker and Novel Target for Therapeutic Intervention on Cancer: A Review

Abstract

Estrogen-related receptors (ERRs), genes similar to estrogen receptors, are identified as hormone-responsive systems associated with the ERR subfamily. These hormone-responsive systems facilitate oncometabolic programs to nourish cancer cell growth, a central node at the interface of cellular energy metabolism and cancer. Several independent studies have implicated ERR isoforms like ERRα, ERRβ, and ERRγ in the pathways of cancer development and progression. The construction of tissue-specific ERR transgenic or knockout mice and the application of synthetic ligands have precisely indicated the critical and diverse role of ERRγ than other isoforms. ERRγ, plays a critical and diverse role, enabling switching metabolism to oncometabolism in favor of cancer cells, making it a “hot target” in cancer therapy. ERRγ expression is correlated with the clinical status of diverse cancer types and various cancer tissue treatments. The dual feature of ERRγ raises interest in understanding its biogenesis and function in different tissues. This review aims to describe the structural organization of ERRs, their central occupancy at the interface of cancer and metabolism, and their biogenesis and expression profile across different cancers. It concludes that ERRγ has potential as a clinical marker in cancer prognosis and a novel non-conventional therapeutic target.