title: Phosphorylation and inactivation of PTEN at residues Ser380/Thr382/383 induced by Helicobacter pylori promotes gastric epithelial cell survival through PI3K/Akt pathway.
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.
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Xie
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
authors.forename: Gongmeizi
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
authors.forename: Ximei
authors.initials: X
authors.lastname: Cao
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.|Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
authors.forename: Shiwen
authors.initials: S
authors.lastname: Luo
authors.affiliation: The Medical College of Nanchang University, Nanchang, Jiangxi, China.|Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
authors.forename: Nonghua
authors.initials: N
authors.lastname: Lu
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000821:virology; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D005753:Gastric Mucosa / Q000378:metabolism; D005756:Gastritis / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000378:metabolism / Q000473:pathology / Q000821:virology; D016480:Helicobacter pylori; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D013270:Stomach / Q000473:pathology*; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000821:virology
chemical_list: D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C494929:PTEN protein, human
keywords: Helicobacter pylori; PI3K/Akt pathway; gastric carcinogenesis; phosphatase and tensin homolog; phosphorylation