Migration of gastric cancer is suppressed by recombinant Newcastle disease virus (rL-RVG) via regulating α7-nicotinic acetylcholine receptors/ERK- EMT

Abstract

Background: 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 (α7-nAChR) overexpression leads to epithelial-mesenchymal transition (EMT) and promotes the migration of gastric cancer cells. Recombinant avirulent LaSota strain of Newcastle disease virus (NDV) expressing the rabies virus glycoprotein (rL-RVG) may promote apoptosis of gastric cancer cells and reduces the migration of lung cancer metastasis. However, whether rL-RVG inhibits migration of gastric cancer cells and what the underlying functional mechanism is remains unknown. Methods: The gastric cancer cell lines BGC and SGC were randomly divided into 3 groups: rL-RVG, NDV and Phosphate Buffered Solution (PBS) control groups. Furthermore,we adopted ACB and MLA,α7nAChR-siRNA for the overexpression and silencing of α7-nAChR.Corynoxenine was used for inhibiting the MEK-ERK pathway. Western blot, Immunofluoresce,cell proliferation assays,cell migration analyses through wound-healing assays and Transwell assays were used to explore the underlying mechanisms. A mouse xenograft model was used to investigate the effects of rL-RVG,NDV on tumor growth. Results: In this study, our findings demonstrate that rL-RVG suppressed the migration of gastric cancer cells and reduced EMT via α7-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 PERK. 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 inhibited nicotinic acetylcholine receptors (nAChRs) to suppress cell migration and epithelial to mesenchymal transition (EMT) in gastric cell. We also found that rL-RVG suppresses the growth of gastric cancer subcutaneous tumor cells in vivo. Conclusion: rL-RVG inhibits α7-nAChR-MEK/ERK-EMT to suppress migration of gastric cancer cells.

Long non-coding RNA AL139002.1 promotes gastric cancer development by sponging microRNA-490-3p to regulate Hepatitis A Virus Cellular Receptor 1 expression

“…YAP has been reported to promote GC cell survival and migration/invasion via the ERK pathway [ 37 ]. Recombinant Newcastle disease virus (rL-RVG) inhibits GC migration by regulating α7-nAChR-MEK/ERK-EMT [ 38 ]. Consistent with previous studies, HAVCR1 was highly expressed in GC cells, and HAVCR1 knockdown induced apoptosis and inhibited proliferation, migration, invasion, and EMT.…”

Not Only Immune Escape—The Confusing Role of the TRP Metabolic Pathway in Carcinogenesis

“…This interaction mainly matters in neuronal disorder, nevertheless, recent reports emphasized the role of nicotinic acetylcholine receptors in oncogenesis. The blockage of a7nAChR reversed acetylcholine-induced cell migration and invasiveness in NSCLC cells and gastric cancer cells via blocking signaling by MEK/ERK pathway [156,157]. Moreover, in gastric cancer, cholangiocarcinoma, this receptor inhibition was connected with reduced expression of EMT markers [158].…”

Development of Molecular Mechanisms and Their Application on Oncolytic Newcastle Disease Virus in Cancer Therapy

“…Furthermore, NDV–GFP may provide a more sensitive method than conventional cytology for detecting gastric cancer. Bu et al, 2019a and Bu et al, 2019b reported that the recombinant LaSota strain expressing rL-RVG (rabies virus glycoprotein) suppressed nAChRs (nicotinic acetylcholine receptors) to reduce cell migration and EMT (epithelial to mesenchymal transition) in gastric cells. Moreover, rL-RVG suppressed the growth of gastric cancer subcutaneous tumor cells in vivo ( Bu et al, 2019a ).…”