G-protein coupled receptor 64 (GPR64) acts as a tumor suppressor in endometrial cancer

Abstract

Background Endometrial cancer is the most common gynecological cancer. G-protein coupled receptor 64 (GPR64) belongs to a family of adhesion GPCRs and plays an important role in male fertility. However, the function of GPR64 has not been studied in endometrial cancer. Our objective is to investigate the role of GPR64 in endometrial cancer. Methods We examined the levels of GPR64 in human endometrioid endometrial carcinoma by immunohistochemistry analysis. To determine a tumor suppressor role of GPR64 in endometrial cancer, we used a siRNA loss of function approach in human endometrial adenocarcinoma cell lines. Results GPR64 levels were remarkably lower in 10 of 21 (47.62%) of endometrial carcinoma samples compared to control. Depletion of GPR64 by siRNA transfection revealed an increase of colony formation ability, cell proliferation, cell migration, and invasion activity in Ishikawa and HEC1A cells. The expression of Connexin 43 ( Cx43 ), a member of the large family of gap junction proteins, was reduced through activation of AMP-activated protein kinase (AMPK) in Ishikawa cells with GPR64 -deficicy. Conclusions These results suggest that GPR64 plays an important tumor suppressor role in endometrial cancer. Electronic supplementary material The online version of this article (10.1186/s12885-019-5998-1) contains supplementary material, which is available to authorized users.

Artificial Intelligence Analysis of Gene Expression Predicted the Overall Survival of Mantle Cell Lymphoma and a Large Pan-Cancer Series

“…G protein-coupled receptor signaling pathway Tumor suppressor in endometrial cancer [84] TYMS Regulation of mitotic cell cycle (G1/S transition) Association with non-Hodgkin lymphomas, prognosis of pancreatic cancer [85,86] The gene information is based on UniProt [54], and Genecards [55]. TYMs was highlighted in Method 2; the rest of genes in Method 1.…”

Emerging roles of adhesion G protein-coupled receptors

“…Interestingly, many of the downstream mediators and effectors of aGPCRs were discovered before their ligands, due to the self-cleavage aspect of their function. For example, ADGRG2 (GPR64) is currently an orphan receptor but due to manual cleavage of its NTD it has been observed to activate G q mobilising intracellular Ca 2+ [ 62 ] and G s stimulating intracellular cAMP production [ 63 ]. ADGRG2 was also found to undergo β-arrestin-mediated endocytosis, further increasing its signalling repertoire by acting as a scaffold for downstream effectors.…”

Function and therapeutic potential of G protein‐coupled receptors in epididymis

“…It is highly expressed in the efferent ductules and the proximal epididymis (Table 1) (Kirchhoff, Osterhoff, & Samalecos, 2008; Obermann et al, 2003). Expression of ADGRG2 has also been detected in parathyroid, prostate, fibroblasts, neuronal and adipose tissue, as well as various types of cancers (Ahn et al, 2019; Balenga et al, 2017; Hamann et al, 2015; Suchy et al, 2020; Xie et al, 2020). Further studies have confirmed the functional importance of ADGRG2 in male fertility.…”