Study on the mechanism of ADGRL4 regulating gastric cancer metastasis through vascular endothelial growth factor signaling pathway
LUO Qingwei
LI Zhihong
TANG Jun
ZHOU Zhijun
YAN Wei
JIANG Xulin
CHEN Xiaoli
HU Gangqiang
Abstract：Objective To explore the mechanism of EGF spider toxin receptor 7th transmembrane domain 1(ADGRL4)regulating gastric cancer metastasis through vascular endothelial growth factor(VEGF)signaling pathway.Methods ADGRL4 expression was detected in normal gastric mucosal epithelial cells and gastric cancer cells after culture.Gastric cancer SGC-7901 cells were divided into control group,overexpression group and silence group.The control group was transfected with empty vector,the overexpression group was transfected with ADGRL4 up-regulated plasmid,and the silent group was transfected with ADGRL4 silent plasmid.To analyze the effects of regulating ADGRL4 expression on invasion,migrate and VEGF signaling pathway protein expression of gastric cancer cells.Results Compared with normal gastric mucosal epithelial cells GES-1,the expression of ADGRL4 in gastric cancer cells SGC-7901,HGC-27 and Hs-746T was increased(P＜0.05).Compared with gastric cancer cells HGC-27 and Hs-746T,the expression level of ADGRL4 in gastric cancer cells SGC-7901 was higher(P＜0.05),so SGC-7901 was selected for follow-up experiment.Compared with the control group,the expression level of ADGRL4 was increased in overexpression group and decreased in silence group(P＜0.05).Compared with the overexpression group,the expression level of ADGRL4 in the silent group was decreased(P＜0.05),indicating successful transfection of ADGRL4.compared with the control group,the invasion number,migrate number,matrix metalloproteinase(MMP)-2,MMP-9,VEGF,vascular endothelial growth factor receptor-2(VEGFR-2)expression of cells in overexpression group increased,while the expression of E-cadherin decreased.The invasion number,migrate number,the expression levels of MMP-2,MMP-9,VEGF and VEGFR-2 decreased in the silent group,while the expression level of E-cadherin increased(P＜0.05).Compared with the overexpression group,the invasion number,migrate number,the expressions of MMP-2,MMP-9,VEGF and VEGFR-2 in the silent group were decreased,and the expression of E-cadherin was increased(P＜0.05).Conclusions After the intervention of down-regulated ADGRL4,the invasion and migrate numbers of gastric cancer cells were reduced,and the expression levels of migration and invasion-related proteins were regulated,which may be related to the inhibition of VEGF pathway.
Keywords：EGF spider toxin receptor 7 transmembrane domain 1Vascular endothelial growth factorGastric cancerTransfer
Publication Date：2024-08-20
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 382-387 )