title: Helicobacter pylori FKBP-type PPIase promotes gastric epithelial cell proliferation and anchorage-independent growth through activation of ERK-mediated mitogenic signaling pathway.
abstract: Though Helicobacter pylori (H. pylori) has been classified as class I carcinogen, key virulence factor(s) generated by H. pylori that causes gastric cancer remains to be fully determined. Here, we show that deletion of peptidyl-prolyl cis-trans isomerase (PPIase) prevented H. pylori from stimulating human gastric epithelial cell (AGS) proliferation. Consistent with this observation, ectopic expression of H. pylori PPIase promoted AGS cell proliferation and anchorage-independent growth. To gain insight into the biochemical mechanism of PPIase-induced effect, early signal events involved in mitogenic signaling pathways were evaluated. Expression of H. pylori PPIase caused an increase in basal as well as EGF-stimulated phosphorylation of ERK and EGF receptor at Tyr1086. Treatment with MEK inhibitor completely blocked PPIase-induced cell proliferation. Our results suggest that H. pylori PPIase has the potential to activate mitogenic signaling pathway and to promote transformation of gastric epithelial cells. H. pylori PPIase may represent a novel target for therapeutic management of gastric cancer patients.
authors: Tumor Etiology and Screening Department, Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China Key Laboratory of Cancer Control in Liaoning province, Shenyang 110001, Liaoning Province, China Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV 26506, USA The Tumor Hospital of Liaoning Province, Shenyang 110001, Liaoning Province, China.
authors: Yanmei
authors: Y
authors: Zhu
authors: Tumor Etiology and Screening Department, Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China Key Laboratory of Cancer Control in Liaoning province, Shenyang 110001, Liaoning Province, China.
authors: Moye
authors: M
authors: Chen
authors: Tumor Etiology and Screening Department, Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China Key Laboratory of Cancer Control in Liaoning province, Shenyang 110001, Liaoning Province, China.
authors: Yuehua
authors: Y
authors: Gong
authors: Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV 26506, USA.
authors: Ziyang
authors: Z
authors: Liu
authors: Tumor Etiology and Screening Department, Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China Key Laboratory of Cancer Control in Liaoning province, Shenyang 110001, Liaoning Province, China.
authors: Aodi
authors: A
authors: Li
authors: Tumor Etiology and Screening Department, Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China Key Laboratory of Cancer Control in Liaoning province, Shenyang 110001, Liaoning Province, China.
authors: Dan
authors: D
authors: Kang
authors: Tumor Etiology and Screening Department, Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China Key Laboratory of Cancer Control in Liaoning province, Shenyang 110001, Liaoning Province, China.
authors: Fang
authors: F
authors: Han
authors: Tumor Etiology and Screening Department, Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China Key Laboratory of Cancer Control in Liaoning province, Shenyang 110001, Liaoning Province, China.
authors: Jingwei
authors: J
authors: Liu
authors: Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV 26506, USA Department of Physiology and Pharmacology, West Virginia University, Morgantown, WV 26506-9229, USA junliu@hsc.wvu.edu.
authors: Jun
authors: J
authors: Liu
authors: Tumor Etiology and Screening Department, Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China Key Laboratory of Cancer Control in Liaoning province, Shenyang 110001, Liaoning Province, China.
authors: Yuan
authors: Y
authors: Yuan
mesh_terms: D017209:Apoptosis; D002460:Cell Line; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism* / Q000382:microbiology; D066246:ErbB Receptors / Q000378:metabolism; D005753:Gastric Mucosa / Q000166:cytology* / Q000378:metabolism / Q000382:microbiology; D017353:Gene Deletion; D016480:Helicobacter pylori / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D006801:Humans; D020935:MAP Kinase Signaling System; D008934:Mitogens; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D013274:Stomach Neoplasms / Q000628:therapy
chemical_list: D008934:Mitogens; D066246:ErbB Receptors; D019696:Peptidylprolyl Isomerase
keywords: ERK; FKBP; Helicobacter pylori; PPIase; gastric cancer; transformation