<em>Helicobacter pylori</em> induces epithelial‑mesenchymal transition in gastric carcinogenesis via the AKT/GSK3β signaling pathway

Ouyang,Yaobin; Liu,Gongmeizi; Xu,Wenting; Yang,Zhen; Li,Nianshuang; Xie,Chuan; Zhou,Chun; Chen,Jiang; Zhu,Yin; Hong,Junbo; Lu,Nonghua

doi:10.3892/ol.2021.12426

February-2021 Volume 21 Issue 2

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February-2021 Volume 21 Issue 2

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Article Open Access

Helicobacter pylori induces epithelial‑mesenchymal transition in gastric carcinogenesis via the AKT/GSK3β signaling pathway

Authors:
- Yaobin Ouyang
- Gongmeizi Liu
- Wenting Xu
- Zhen Yang
- Nianshuang Li
- Chuan Xie
- Chun Zhou
- Jiang Chen
- Yin Zhu
- Junbo Hong
- Nonghua Lu
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Affiliations: Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Urology, The Haidian Hospital of Beijing, Beijing 100700, P.R. China

Copyright: © Ouyang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Article Number: 165
|
Published online on: January 4, 2021

https://doi.org/10.3892/ol.2021.12426
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Abstract

Helicobacter pylori (H. pylori) is a main risk factor for gastric cancer (GC). Epithelial‑mesenchymal transition (EMT) is involved in the development and progression of H. pylori‑associated GC. However, the exact molecular mechanism of this process remains unclear. The AKT/GSK3β signaling pathway has been demonstrated to promote EMT in several types of cancer. The present study investigated whether H. pylori infection induced EMT, and promoted the development and metastasis of cancer in the normal gastric mucosa, and whether this process was dependent on AKT activation. The expression levels of the EMT‑associated proteins, including E‑cadherin and N‑cadherin, were determined in 165 gastric mucosal samples of different disease stages by immunohistochemical analysis. The expression levels of E‑cadherin, N‑cadherin, AKT, phosphorylated (p‑)AKT (Ser473), GSK3β and p‑GSK3β (Ser9) were further determined in H. pylori‑infected Mongolian gerbil gastric tissues and cells co‑cultured with H. pylori by immunohistochemical analysis and western blotting. The results indicated that the expression levels of the epithelial marker E‑cadherin were decreased, whereas the expression levels of the mesenchymal marker N‑cadherin were increased during gastric carcinogenesis. Their expression levels were associated with H. pylori infection. Furthermore, H. pylori infection resulted in downregulation of E‑cadherin expression and upregulation of N‑cadherin expression in Mongolian gerbils and GES‑1 cells. In addition, an investigation of the associated mechanism of action revealed that p‑AKT (Ser473) and p‑GSK3β (Ser9) were activated in GES‑1 cells following co‑culture with H. pylori. Furthermore, following pretreatment of the cells with the AKT inhibitor VIII, the expression levels of E‑cadherin, N‑cadherin, p‑AKT and p‑GSK3β did not show significant differences between GES‑1 cells that were co‑cultured with or without H. pylori. The levels of p‑AKT and p‑GSK3β were increased in H. pylori‑infected Mongolian gerbils. In conclusion, the present study demonstrated that H. pylori infection activated AKT and resulted in the phosphorylation and inactivation of GSK3β, which in turn promoted early stage EMT. These effects were AKT‑dependent. This mechanism may serve as a prerequisite for GC development.

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