Phosphorylation and inactivation of PTEN at residues Ser380/Thr382/383 induced by Helicobacter pylori promotes gastric epithelial cell survival through PI3K/Akt pathway.

// Zhen Yang 1 , Chuan Xie 1 , Wenting Xu 1 , Gongmeizi Liu 1 , Ximei Cao 1 , Wei Li 1 , Jiang Chen 1 , Yin Zhu 1 , Shiwen Luo 1,2 , Zhijun Luo 3,4 and Nonghua Lu 1 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 Correspondence to: 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 Abstract 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.