Expression of GPR68, an Acid-Sensing Orphan G Protein-Coupled Receptor, in Breast Cancer

Abstract

BackgroundBreast cancer (BC) is the most diagnosed cancer and the leading cause of global cancer incidence in 2020. It is quite known that highly invasive cancers have disrupted metabolism that leads to the creation of an acidic tumor microenvironment. Among the proton-sensing G protein-coupled receptors is GPR68. In this study, we aimed to explore the expression pattern of GPR68 in tissues from BC patients as well as different BC cell lines. Methods: In-silico tools were used to assess the expression of GPR68 in BC patients. The expression pattern was validated in fresh and paraffin-embedded sections of BC patients using qPCR and immunohistochemistry (IHC), respectively. Also, in-silico tools investigated GPR68 expression in different BC cell lines. Validation of GPR68 expression was performed using qPCR and immunofluorescence techniques in four different BC cell lines (MCF-7, MDA-MB-231, BT-549 and SkBr3). Results: GPR68 expression was found to be significantly increased in BC patients using the in-silico tools and validation using qPCR and IHC. Upon classification according to the molecular subtypes, the luminal subtype showed the highest GPR68 expression followed by triple-negative and Her2-enriched cells. However, upon validation in the recruited cohort, the triple-negative molecular subtype of BC patients showed the highest GPR68 expression. Also, in-silico and validation data revealed that the triple-negative breast cancer cell line MDA-MB-231 showed the highest expression of GPR68. Conclusion: Therefore, this study highlights the potential utilization of GPR68 as a possible diagnostic and/or prognostic marker in BC.

Elucidating the activation mechanism of the proton-sensing GPR68 receptor

“…This receptor is coupled with different types of G- proteins 1,3,4 and is involved in a variety of biological processes including cellular differentiation in bone tissue 5,6 , regulation of insulin levels 7 , mechanosensing 8,9 , hippocampal neurogenesis 10 , memory 11 and hormone release from the pituitary gland 12,13 . GPR68 has also been shown to have a role in tumour growth 4,14–18 and metastasis 19,20 , and has been found in many neoplastic tissues 21 , possibly associated with the microacidic environment involved in solid tumours 22 .…”

Recent advances in acid sensing by G protein coupled receptors

“…Research published in the past few years adds to the complicated picture. Several studies have investigated OGR1 in cancer, specifically in pancreatic, breast, ovarian, skin, liver, head and neck, colorectal and oesophageal cancer [ 5 , 6 , 14 , 18 , 30 , 33 , 48 , 54 , 63 , 77 , 78 , 88 , 96 , 98 , 101 ], ranging from pure expression (e.g. [ 5 , 48 ]) to functional studies in cells (e.g.…”

Puzzling out the role of MIAT LncRNA in hepatocellular carcinoma

“…An important hallmark of cancer in general and HCC in particular is the immune escape [ 14 , 16 , 21 , 22 , 113 , 114 ]. Immune cells, infiltrating the tumor microenvironment (TME), have an enormous impact in stopping the tumor cells from proliferation, invasion, and dissemination [ [115] , [116] , [117] ]. Another considerable barrier in HCC therapeutic protocols is high incidence rates of resistance to the conventional anticancer agents that would consequently lead to more aggressive tumors and a rapid relapse in many cases [ 50 , 118 ].…”