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《Journal of Third Military Medical University》 2012-01
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Effect of crosstalk between EGFR and integrin signaling pathways on invasion of gastric cancer cells

Ding Jian1,Li Dan2,Lin Na2,Wang Xiaozhong2,Wang Chengdang1,Wu Ting1(1Department of Enterology,First Affiliated Hospital,Fujian Medical University,Fuzhou,Fujian Province,350005;2Department of Enterology,Union Hospital of Fujian Medical University,Fuzhou,Fujian Province,350001,China)  
Objective To understand crosstalk between epidermal growth factor receptor(EGFR) and integrin signaling pathways and effect of the crosstalk on cell invasion and proliferation in human gastric cancer cell SGC7901.Methods Human gastric cancer cells SGC7901 were stimulated with EGF and Fn,respectively.Protein expressions of total and phosphorylated ERK,FAK(Y397) and p130cas(Y410) were measured by immunoprecipitation and Western blotting.Invasion and proliferation of gastric cancer cells were detected by modified Boyden chamber and MTT assay.RNA interference was used to block FAK expression,and the effect of low level of FAK on cross reaction,cell invasion and proliferation were testified.Results Expressions of total ERK,FAK and p130cas had no significant change before and after stimulation.After stimulation with Fn,tyrosine phosphorylated ERK increased 2.90 times(P0.05);cell invasiveness enhanced 2.36 times(P0.05);and MTT value at 24 h increased 1.68 times(P0.05).After stimulation with EGF,phosphorylated FAK(Y397) increased 2.75 times(P0.05);phosphorylated p130cas(Y410) increased 4.33 times(P0.05);cell invasiveness increased 1.50 times(P0.05);and MTT value at 24 h increased 1.76 times(P0.05).In cells transfected with FAK siRNA,FAK(Y397) phosphorylation was only 0.30 times of the control(P0.05).After stimulation with Fn,ERK tyrosine phosphorylation was only 0.66 times of the control(P0.05);cell invasiveness was only 0.37 of the control(P0.05);and MTT value at 24 h was only 0.63 times of the control(P0.05).After stimulation with EGF,p130(Y410) phosphorylation was only 0.49 times of the control(P0.05);cell invasiveness was only 0.48 times of the control(P0.05);and MTT value at 24 h was only 0.77 times of the control(P0.05).Conclusion There is a crosstalk between EGFR and integrin signaling pathways in human gastric cancer cell SGC7901.FAK,which is a key module in the crosstalk,its inhibition can reduce invasion and proliferation of human gastric cancer cells induced by crosstalk between EGFR and integrin.
【Fund】: 福建省自然科学基金(2009J01148);; 福建省卫生厅创新基金(2009-CXB-14);; 福建医科大学苗圃科研基金(2010MP033)~~
【CateGory Index】: R735.2
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