Crosstalk between EGFR and integrin affects invasion and proliferation of gastric cancer cell line, SGC7901
Li Dan,1,* Ding Jian,2,* Lin Na,1 Wang Xiaozhong,1
1Digestive Department, the Union Hospital of Fujian Medical University, Fujian, People’s Republic of China; 2Digestive Department, the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China
*These authors contributed equally to this work
Background/objective: To investigate the crosstalk between epidermal growth factor receptor (EGFR) and integrin-mediated signal transduction pathways in human gastric adenocarcinoma cells.
Methods: EGF was used as a ligand of EGFR to stimulate the gastric adenocarcinoma cell, SGC7901. Signal molecules downstream of the integrin, FAK(Y397) and p130cas(Y410) phosphorylation, were measured by immunoprecipitation and western blot. Fibronectin (Fn) was used as a ligand of integrin to stimulate the same cell line. Signal molecules downstream of EGFR and extracellular signal-regulated kinase (ERK) general phosphorylation were also measured. Focal adhesion kinase (FAK) small-interfering RNA was designed and transfected into SGC7901 cells to decrease the expression of FAK. Modified Boyden chambers and MTT assay were used to examine the effect of FAK inhibition on the invasiveness and proliferation of SGC7901.
Results: EGF activated FAK(Y397) and p130cas(Y410) phosphorylation, while Fn activated ERK general phosphorylation. Inhibition of FAK expression decreased p130cas(Y410) phosphorylation activated by EGF and ERK general phosphorylation activated by Fn, also decreased the invasiveness and proliferation of SGC7901 cells activated by EGF or Fn.
Conclusion: There is crosstalk between EGFR and integrin signal transduction. FAK may be a key cross point of the two signal pathways and acts as a potential target for human gastric cancer therapy.
Keywords: gastric adenocarcinoma, epidermal growth factor receptor, integrin, focal adhesion kinase, crosstalk
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