G Protein-Coupled Receptors (GPCRs)-Mediated Calcium Signaling in Ovarian Cancer: Focus on GPCRs activated by Neurotransmitters and Inflammation-Associated Molecules

Abstract

G-coupled protein receptors (GCPR) involve several signaling pathways, some of them being coupled with intracellular calcium (Ca2+) mobilization. GPCRs were involved in migration, invasion and metastasis of different types of cancers, including ovarian cancer. Many studies have discussed the essential contribution of GPCRs activated by steroid hormones in ovarian cancer. However, ovarian cancer is also associated with altered signals coming from the nervous system, the immune system or the inflammatory environment, in which GPCRs are ‘sensing’ these molecular signals. Many studies have been oriented so far on ovarian cell lines (most of them being of human cell lines), and only few studies based on animal models or clinical studies have been devoted to the expression changes or functional role of GPCRs in ovarian cancer. In this paper, we review the alterations of GPCRs activated by neurotransmitters (muscarinic receptors, serotonin receptors, dopamine receptors, adrenoceptors) or inflammation-associated molecules (bradykinin receptors, histamine receptors, chemokine receptors) in ovarian cancer and we discuss their potential as histological biomarkers.

Methiothepin Suppresses Human Ovarian Cancer Cell Growth by Repressing Mitochondrion-Mediated Metabolism and Inhibiting Angiogenesis In Vivo

“…However, most patients receiving paclitaxel and platinum-based drugs experience relapse [ 4 ]. Mechanisms determining the prognosis of ovarian cancer are not yet clear, but various hormones, growth factors, and neurotransmitters are reported to activate receptor-mediated growth signals in ovarian cancer cells [ 5 , 16 , 17 ]. Therefore, antagonists of receptors that contribute to the activation of growth signals have potential as therapeutic adjuncts to ovarian cancer [ 18 , 19 ].…”

“…In ovarian cancer, G protein coupled receptor (GPCR)-dependent Ca 2+ signaling is reported to be activated by many types of neurotransmitters [ 5 ]. Alteration in the signaling cascades by activation of GPCRs contributes to cell proliferation, angiogenesis, and metastasis in various cancer types including ovarian cancer [ 6 ].…”

Altered Organelle Calcium Transport in Ovarian Physiology and Cancer

“…Such signals can be induced by muscarinic, adrenergic, serotoninergic, dopaminergic, bradykinine, histamine, and chemokine receptors, many of which mediate Ca 2+ signaling. Although these mechanisms have not been extensively studied, they provide promising leads for future perspectives regarding ovarian cancer management [ 41 ]. The role of Ca 2+ transients via GPCRs in ovarian cancer has been investigated in several studies analyzing the effects of various stimuli on ovarian cancer cell lines, as summarized in Table 3 .…”

“…Calcium signaling alterations [ 40 , 41 , 42 ] or signaling pathway network alterations [ 1 , 43 ] in ovarian cancer have previously been analyzed, with most studies focusing on calcium signaling pathways triggered by ion channels/receptors/pumps from the plasma membrane. However, a systematic overview of calcium signaling alterations in organelles in ovarian cancer is largely missing.…”

d,l-Methadone causes leukemic cell apoptosis via an OPRM1-triggered increase in IP3R-mediated ER Ca2+ release and decrease in Ca2+ efflux, elevating [Ca2+]i

“…Activation of opioid GPCRs induces conformational change in the receptor that facilitates the exchange of GDP for GTP on G α , leading to uncoupling from G βγ 17 . Uncoupled GTP-bound G α and G βγ dimer regulate diverse physiological functions including apoptosis 5 through stimulation of their downstream effectors such as cyclic adenosine monophosphate (cAMP) and Ca 2+ 18 . As with other GPCRs, opioid receptors bind to G α subunits, including members of the G αi/o family 19 , 20 .…”