Cancer is a major public health issue and represents the second leading cause of death in women worldwide, as female reproductive-related
neoplasms are the main cause of incidence and mortality. Female reproductive
cancers have a close relationship to
estrogens, the principal female
sex steroid hormones.
Estrogens exert their actions by the nuclear
estrogen receptor alpha (ERα) and
estrogen receptor beta (ERβ). ERα, and ERβ act as
transcription factors mediating genomic effects. Besides, the
G protein-coupled
estrogen receptor (GPER, formerly known as GPR30) was recently described as a seven-transmembrane receptor that mediates non-genomic estrogenic signaling, including
calcium mobilization, cAMP synthesis, cleavage of
matrix metalloproteinases, transactivation of
epidermal growth factor receptor (EGFR), and the subsequent activation of PI3K and MAPK signaling pathways, which are the reasons why it is related to cellular processes, such as cell-cycle progression, cellular proliferation, differentiation, apoptosis, migration, and invasion. Since its discovery, selective agonists and antagonists have been found and developed. GPER has been implicated in a variety of
hormone-responsiveness
tumors, such as breast, endometrial, ovarian, cervical, prostate, and
testicular cancer as well as lung, hepatic, thyroid, colorectal, and
adrenocortical cancers. Nevertheless, GPER actions in
cancer are still debatable due to the conflicting information that has been reported to date, since many reports indicate that activation of this receptor can modulate
carcinogenesis. In contrast, many others show that its activation inhibits
tumor activity. Besides,
estrogens play an essential role in the regulation of the immune system, but little information exists about the role of GPER activation on its modulation within
cancer context. This review focuses on the role that the stimulation of GPER plays in female reproductive
neoplasms, specifically breast, endometrial, ovarian, and
cervical cancers, in its
tumor activity and immune response regulation.