Gastrin-17 induces gastric cancer cell epithelial-mesenchymal transition via the Wnt/β-catenin signaling pathway

Abstract

Gastric cancer (GC) is one of the most common cancers, with most patients often succumbing to death as a result of tumor metastasis. Recent work has demonstrated that gastrin is closely associated with GC metastasis. However, the specific molecular mechanisms underlying this relationship remain to be unveiled. In this study, we assessed the impact of gastrin and the Wnt/β-catenin inhibitor XAV939 on the epithelial-mesenchymal transition (EMT) of the SGC-7901 and MKN45 GC cell lines, and we determined that gastrin-17 significantly decreased E-cadherin expression and upregulated the expression of Snail1 and N-cadherin in GC cells. In addition, gastrin 17 also significantly increased the expression of Wnt3α in a dose-dependent manner. Consistent with these results, gastrin-17 promoted GC cell invasion, proliferation, and migration in a dose-dependent fashion, and these effects were inhibited by XAV939. Together, these results indicated that gastrin-17 induced GC cell EMT, migration, and invasion via the Wnt/β-catenin signaling pathway, which suggests that this gastrin/Wnt/β-catenin signaling axis may represent a therapeutic target for the prevention of GC metastasis.

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Acknowledgements

The authors are grateful to the editor, the associate editor, and the reviewer. We thank International Science Editing ( http://www.internationalscienceediting.com ) for editing this manuscript.

Funding

The work was supported by National Natural Science Foundation of China (31660031, 31760328, 31960028), Project of Science and Technology of Guiyang (ZhuKeHe[2017]30-4), Guizhou Science and Technology Innovation Talent Team [2017]5652)

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Authors

Contributions

Yuan Xie and JianJiang Zhou conceived and designed the experiments. YaJie Li, Yan Zhao, Yi Li, XiaoYi Zhang, and Chao Li performed the experiments and analyzed the data. NiYa Long, XueShu Chen, and LiYa Bao gave intellectual advice and revised the manuscript. Yuan Xie and YaJie Li wrote the paper.

Corresponding author

Correspondence to Yuan Xie.

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The project was approved by the Ethics Committee of The Guizhou Medical University. The authors declare that they have no conflict of interest.

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Key Points

(1) Gastrin-17 promotes EMT, proliferation, migration, and invasion.

(2) Gastrin-17 activates the Wnt/β-catenin signaling pathway.

(3) Gastrin-17 promotes EMT via the Wnt/β-catenin pathway.

Supplementary Information

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Li, Y., Zhao, Y., Li, Y. et al. Gastrin-17 induces gastric cancer cell epithelial-mesenchymal transition via the Wnt/β-catenin signaling pathway. J Physiol Biochem 77, 93–104 (2021). https://doi.org/10.1007/s13105-020-00780-y

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Keywords

  • Gastric cancer
  • Gastrin-17
  • Epithelial-mesenchymal transition
  • Wnt/β-catenin
  • Malignant