Gastrin promotes the metastasis of gastric carcinoma through the β-catenin/TCF-4 pathway

Zhuang,Kun; Yan,Yuan; Zhang,Xin; Zhang,Jun; Zhang,Lingxia; Han,Kun

doi:10.3892/or.2016.4943

Gastrin promotes the metastasis of gastric carcinoma through the β-catenin/TCF-4 pathway

Authors:
- Kun Zhuang
- Yuan Yan
- Xin Zhang
- Jun Zhang
- Lingxia Zhang
- Kun Han
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Affiliations: Division of Gastroenterology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710003, P.R. China, Division of Gastroenterology, Xi'an Central Hospital, Xi'an, Shaanxi 710003, P.R. China
Published online on: July 15, 2016 https://doi.org/10.3892/or.2016.4943
Pages: 1369-1376

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Abstract

Gastric cancer is the most common epithelial malignancy and the second leading cause of cancer-related death worldwide; metastasis is a crucial factor in the progression of gastric cancer. The present study applied gastrin-17 amide (G-17) in SGC7901 cells. The results showed that G-17 promoted the cell cycle by accelerating the G0/G1 phase and by increasing the cell proliferation rate by binding to the gastrin receptor. The migratory and invasive abilities of the SGC7901 cells were increased by G-17. The expression levels of matrix metalloproteinase (MMP)-7, MMP-9 and vascular endothelial growth factor (VEGF) were enhanced by G-17 as well. Moreover, G-17 caused the overexpression of β-catenin and TCF-4. G-17 also caused a preferential cytoplasmic and nuclear localization of β-catenin with a high TOP-FLASH activity. Finally, axin reduced the migratory and invasive abilities of the SGC7901 cells, and inhibited the expression of β-catenin, TCF-4, MMP-7, MMP-9 and VEGF; these effects were counteracted by adding G-17. In summary, the present study confirmed the proliferation and metastasis-promoting role of G-17 via binding to the gastrin receptor, and the β-catenin/TCF-4 pathway was found to be essential for mediating G-17-induced metastasis in gastric cancer. These results may provide a novel gene target for the treatment of gastric cancer.

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