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

GPR56 通过激活 PI3K/AKT 信号促进结直肠癌细胞增殖并通过上皮间质转化增强转移

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作者:Bing Ji, Yifei Feng, Ye Sun, Dongjian Ji, Wenwei Qian, Zhiyuan Zhang, Qingyuan Wang, Yue Zhang, Chuan Zhang, Yueming Sun

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.

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