Abstract
It is well established that gastrointestinal (GI) cancers are common and devastating diseases around the world. Despite the significant progress that has been made in the treatment of GI cancers, the mortality rates remain high, indicating a real need to explore the complex pathogenesis and develop more effective therapeutics for GI cancers. G protein-coupled receptors (GPCRs) are critical signaling molecules involved in various biological processes including cell growth, proliferation, and death, as well as immune responses and inflammation regulation. Substantial evidence has demonstrated crucial roles of GPCRs in the development of GI cancers, which provided an impetus for further research regarding the pathophysiological mechanisms and drug discovery of GI cancers. In this review, we mainly discuss the roles of sphingosine 1-phosphate receptors (S1PRs), angiotensin II receptors, estrogen-related GPCRs, and some other important GPCRs in the development of colorectal, gastric, and esophageal cancer, and explore the potential of GPCRs as therapeutic targets.
Highlights
Gastrointestinal (GI) cancers are common and devastating diseases with high global incidence and prevalence rates
We mainly focus on the roles of sphingosine 1-phosphate receptors, angiotensin II receptors, estrogen-related G protein-coupled receptors (GPCRs), and some other important GPCRs in Colorectal cancer (CRC) (Table 1)
Gao et al [73] found that migrating cancer stem cells (MCSCs) were expressed in CRC tissues and CRC cell lines. They identified CD110+ and CDCP1+ MCSCs as candidate markers of organ-specific metastasis. In line with this finding, other studies further suggested that AT1R and AT2R were expressed on two subpopulations of CSCs (SOX2+ and OCT4+) in tissues of colon adenocarcinoma metastasis to the liver (CAML) [9,74]
Summary
Gastrointestinal (GI) cancers are common and devastating diseases with high global incidence and prevalence rates. GI cancers show sexual dimorphism in incidence and mortality, which has attracted considerable interest in evaluating roles of estrogen and estrogen-related GPCRs in the initiation and development of GI cancers including colorectal, gastric, and esophageal cancer [1,12,13,14] These estrogen-related GPCRs and associated signaling pathways regulate TME and EMT, the characteristic features of cancers, modulating cancer behavior and the antitumoral therapy response [15,16]. From this point, estrogen-related GPCRs are appealing therapeutic targets for GI cancer. We evaluate the therapeutic potential of targeting GPCRs and the associated signaling pathways in the prevention and treatment of GI cancers
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