Phosphorylation and inactivation of PTEN at residues Ser380/Thr382/383 induced by Helicobacter pylori promotes gastric epithelial cell survival through PI3K/Akt pathway
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Zhen Yang1, Chuan Xie1, Wenting Xu1, Gongmeizi Liu1, Ximei Cao1, Wei Li1, Jiang Chen1, Yin Zhu1, Shiwen Luo1,2, Zhijun Luo3,4 and Nonghua Lu1
1 Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
2 Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
3 The Medical College of Nanchang University, Nanchang, Jiangxi, China
4 Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA
Nonghua Lu, email:
Keywords: gastric carcinogenesis, Helicobacter pylori, phosphatase and tensin homolog, phosphorylation, PI3K/Akt pathway
Received: March 31, 2015 Accepted: August 19, 2015 Published: September 10, 2015
Phosphorylation of PTEN at residues Ser380/Thr382/383 leads to loss of phosphatase activity and tumor suppressor function. Here, we found that phosphorylation of PTEN at residues Ser380/Thr382/383 was increased with gastric carcinogenesis, and more importantly, Helicobacter pylori was a trigger of this modification in chronic non-atrophic gastritis. H. pylori could phosphorylate and inactivate PTEN in vivo and in vitro, resulting in survival of gastric epithelial cells. Furthermore, stable expression of dominant-negative mutant PTEN or inhibition of Akt prevented the enhanced survival induced by H. pylori. These results indicate that PTEN phosphorylation at residues Ser380/Thr382/383 is a novel mechanism of PTEN inactivation in gastric carcinogenesis, and H. pylori triggers this modification, resulting in activation of the PI3K/Akt pathway and promotion of cell survival.
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