Multifaceted Networking of The Orphan Receptor Estrogen-Related Receptor Β in Breast Cancer Progression

Abstract

Breast cancer death polls are rising at an alarming rate in females globally. It is a hormone-dependent disease that is majorly regulated by estrogen. Several genetic and environmental factors are the primary attributes of breast cancer growth and development. A higher proportion of breast cancer patients harbor estrogen receptor-positive (ER+ve) status. Estrogen related receptors are orphan nuclear receptors which include ERRα, ERRβ, and ERRϒ that exhibit a sequence similarity with ERα. ERRα and ERRϒ act as activators in cancer. ERRβ expression is downregulated in breast cancer cells and patient samples, compared to healthy breast cells. The decreased expression of ERRβ is primarily mediated by the proteasomal pathway at the protein level. ERRβ restricts cell cycle progression in breast cancer cells, thereby impeding breast cancer proliferation. Neddylation of ERRβ mediates its downregulation which triggers the oncogenic signalling in breast cancer. Our study showed employing MLN4924, an NAE inhibitor to restore the expressivity of ERRβ could provide a successful and cutting-edge therapeutic method. This review article illustrates the regulatory role of ERRβ in the formation and evolution of breast cancer, making it an effective therapeutic candidate.