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Chinese Archives of General Surgery(Electronic Edition) ›› 2020, Vol. 14 ›› Issue (04): 248-252. doi: 10.3877/cma.j.issn.1674-0793.2020.04.003

Special Issue:

• Original Article • Previous Articles     Next Articles

CXCL1 promoting the metastases of gastric cancer via integrin β1

Zhewei Wei1, Changhua Zhang2, Yulong He3,()   

  1. 1. Department of Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
    2. Department of Digestive Diseases, the Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518000, China
    3. Department of Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China; Department of Digestive Diseases, the Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518000, China
  • Received:2020-03-13 Online:2020-08-01 Published:2020-08-01
  • Contact: Yulong He
  • About author:
    Corresponding author: He Yulong, Email:

Abstract:

Objective

To investigate the effect of CXCL1 on the migration of gastric cancer (GC) cells and its potential mechanism.

Methods

Lentivirus particles expressing CXCL1 were constructed to establish a stable CXCL1 overexpressing SGC-7901 cell line (7901-CXCL1-GFP) and BGC-823 cell line (823-CXCL1-GFP). siRNA was utilized to block the expression of CXCL1 and integrin β1 in SGC-7901 and BGC-823 cells. Western blotting was performed to analyze the expression of CXCL1, integrin β1, FAK,SRC, ERK, MMP-2 and MMP-9. Transwell assays were adopted to evaluate the migration of gastric cancer cells.

Results

The expression of integrin β1 was higher in 7901-CXCL1-GFP and 823-CXCL1-GFPcells than that in 7901-GFP and 823-GFP cells. Integrin β1 expression was down-regulated by blocking CXCL1 with siRNA. Blocking integrin β1 by siRNA could inhibit CXCL1-induced migration of SGC-7901and BGC-823 cells. CXCL1 increased the expression of p-FAK, p-SRC and p-ERK in GC cells, which could be blocked by integrin β1 knockdown with siRNA. CXCL1 induced the expression of MMP-2 and MMP-9 in GC cells through integrin β1 signaling, meanwhile knockdown of integrin β1 inhibited the MMP-2 and MMP-9 expression. GM6001, one MMPs inhibitor, significantly reduced CXCL1-induced migration of 7901-CXCL1-GFP and 823-CXCL1-GFP cells (P<0.05).

Conclusion

Overexpressed CXCL1 promotes migration of GC cells by activating FAK-SRC-ERK pathway and regulating the expression of MMP-2, MMP-9 through integrin β1 signaling.

Key words: Gastric Cancer, Chemokines, CXCL1, Integrin β1

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