GPR56 promotes proliferation of colorectal cancer cells and enhances metastasis via epithelial‑mesenchymal transition through PI3K/AKT signaling activation

Abstract

G protein-coupled receptor 56 (GPR56), a member of the orphan GPCR family, has been reported to be an oncogene in various malignancies. However, little is known regarding the detailed molecular mechanism of GPR56 in colorectal cancer (CRC). The present study aimed to detect the expression level and biological function of GPR56 in CRC. We examined the expression of GPR56 in CRC tissues and cell lines by quantitative real time (qRT)-PCR, immunohistochemistry, and western blot analysis. The prognostic significance of GPR56 in CRC patients was evaluated by Kaplan-Meier survival analysis. The influence of GPR56 on tumor cell proliferation (via Cell Counting Kit-8, and a tumor formation assay in mice), apoptosis (flow cytometry), cell cycle distribution (flow cytometry) and migration (Transwell assay) was explored. We also investigated the underlying mechanism of GPR56 by western blot analysis. We found GPR56 expression was significantly upregulated in CRC tissues and cell lines compared to corresponding normal controls. Higher GPR56 expression in patients predicted poorer prognosis. Depletion of GPR56 markedly suppressed cell proliferation, migration, and invasion. GPR56 overexpression promoted CRC cell metastasis by expediting epithelial-mesenchymal transition by activating PI3K/AKT signaling. In conclusion, GPR56 played an important role in CRC progression and may represent a new therapeutic target to reduce CRC metastasis.

The Effect of 3′-Hydroxy-3,4,5,4′-Tetramethoxy -stilbene, the Metabolite of the Resveratrol Analogue DMU-212, on the Motility and Proliferation of Ovarian Cancer Cells

“…GPR56, a member of the orphan G protein-coupled receptors (GPCRs) family, has been shown to be an oncogene in various types of cancer. Several studies have revealed that GPR56 overexpression promoted the invasion of cancer cells, whereas depletion of GPR56 remarkably inhibited cell proliferation, migration, and metastasis [37]. Our results are in agreement with the other authors' findings since we showed that decreased expression of GPR56 triggered by DMU-214 was accompanied by suppression of motility of SKOV-3 cells.…”

“…Our results are in agreement with the other authors' findings since we showed that decreased expression of GPR56 triggered by DMU-214 was accompanied by suppression of motility of SKOV-3 cells. As more than 30% of anticancer drugs currently target GPCRs [37], the inhibition of GPR56 expression by DMU-214 seems to provide a promising approach to the treatment of cancer.…”

SPNS2 promotes the malignancy of colorectal cancer cells via regulating Akt and ERK pathway

“…Akt signalling pathway is critical in modulating CRC malignancy. Some functional proteins and natural active molecules have been reported to regulate proliferation, apoptosis, migration and invasion of CRC cells through Akt pathway …”

“…Some functional proteins and natural active molecules have been reported to regulate proliferation, apoptosis, migration and invasion of CRC cells through Akt pathway. [8][9][10][11] Sphingosine-1-phosphate (S1P) is a lipid mediator derived from sphingosine and is catalyzed by two sphingosine kinases (SPHK1 and SPHK2). 12,13 S1P is involved in immune response and cancer progression by binding to G protein-coupled receptors 1-5 (S1PR1-S1PR5).…”

Adhesion G-protein coupled receptors: Implications for metabolic function

“…It has been reported that aGPCRs expressed in the GI tract include GPR56, GPR126, GPR128, CD97, LPHN2 and CELSR1 (Fagerberg et al, 2013;Hamman et al, 2015). However, the role, if any, that GI tract aGPCRs play in regulating fuel homeostasis is currently unknown and most studies to date have focused on their contribution to colorectal carcinoma (Hilbig et al, 2018;Ji et al, 2018).…”