Unraveling the role of GPER in breast cancer

The G protein-coupled estrogen receptor-1 (GPER, formerly called GPR30) has been recently involved in the multifaceted transduction pathways through which estrogens induce diverse biological responses as well as pathological processes, including cancer development and progression. In this regard, it has been shown that not only estrogens but also antiestrogens binding to and activating the GPER-dependent signaling elicit stimulatory effects in hormone-dependent tumors like breast cancer. In accordance with these findings, GPER expression was associated with worse clinical features commonly used to assess the progression of breast malignancies, such as the detection of distant metastases. On the basis of diverse studies demonstrating the potential role of GPER in mediating the stimulatory action of estrogens in breast tumor, GPER may be considered as a valuable target toward novel therapeutic strategies against the development of breast cancer. Furthermore, the promiscuous activity exerted by antiestrogens, which act as GPER agonists and antagonists of the nuclear estrogen receptors, addresses the need of new selective estrogen receptor inhibitors.