Migration of gastric cancer is suppressed by rabies virus glycoprotein via regulating α7-nicotinic acetylcholine receptors/ERK-EMT

Abstract

Nicotinic acetylcholine receptors (nAChRs) have been reported to be overexpressed in malignancies in humans and is associated with tumorigenesis and cell migration. In previous studies of gastric cancer, alpha7 nicotinic acetylcholine receptor (7-nAChR) overexpression can induce epithelial-mesenchymal transition (EMT) and promote migration of gastric cancer cells. Recombinant avirulent Newcastle disease virus (NDV) LaSota strain expressing the rabies virus glycoprotein (rL-RVG) may promote apoptosis of gastric cancer cells and reduces migration of lung cancer metastasis. However, whether rL-RVG inhibits migration of gastric cancer cells and what the underlying functional mechanism is remains unknown. In this study, our findings demonstrate that rL-RVG suppressed migration and reduced EMT of gastric cancer cells via 7-nAChR in vitro. Furthermore rL-RVG decreased the phosphorylation levels of the MEK/ERK signaling pathway such as down-regulating the expression of P-MEK and P-ERK. Additionally, rL-RVG also reduced the expression level of mesenchymal markers N-cadherin and Vimentin and enhanced the expression of the epithelial marker E-cadherin. Lastly, rL-RVG together with nicotinic acetylcholine receptors (nAChRs) inhibited gastric cancer epithelial to mesenchymal transition (EMT) which suppressed gastric cancer cell migration. We also found that rL-RVG suppresses the growth of gastric cancer subcutaneous tumor cells in vivo. Thus, rL-RVG inhibits 7-nAChR-MEK/ERK-EMT to suppress migration of gastric cancer cells.