title: p27(kip1) upregulated by hnRNPC1/2 antagonizes CagA (a virulence factor of Helicobacter pylori)-mediated pathogenesis.
abstract: OBJECTIVE
  Infection by Helicobacter pylori is one of the major contributing factors of chronic active gastritis and peptic ulcer and is closely associated with the occurrence and progression of gastric cancer. CagA protein is a major virulence factor of H. pylori that interacts with SHP-2, a true oncogene, to interfere with cellular signaling pathways; CagA also plays a crucial role in promoting the carcinogenesis of gastric epithelial cells. However, currently, the molecular mechanisms of gastric epithelial cells that antagonize CagA pathogenesis remain inconclusive.
  
  
  METHODS
  We showed that AGS gastric cancer cells transfected with CagA exhibited the inhibition of proliferation and increased activity of caspase 3/7 using two-dimensional gel electrophoresis and secondary mass spectrometry (MS/MS).
  
  
  RESULTS
  It was found that the AGS gastric cancer cells stably expressing CagA displayed significantly increased the expression of 16 proteins, including hnRNPC1/2. Further analysis revealed that hnRNPC1/2 significantly boosted the expression of the p27(kip1) protein.
  
  
  CONCLUSIONS
  Our data suggested that hnRNPC1/2 upregulates p27(kip1) expression and the subsequent suppression of cell proliferation and induction of apoptosis, thereby providing an important mechanism whereby gastric epithelial cells antagonize CagA-mediated pathogenesis.
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Department of Laboratory Medicine, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China.
authors.forename: Shenghang
authors.initials: S
authors.lastname: Jin
authors.forename: Minjin
authors.initials: M
authors.lastname: Wu
authors.forename: Hanqin
authors.initials: H
authors.lastname: Cao
authors.forename: Sunke
authors.initials: S
authors.lastname: Ying
authors.forename: Jiping
authors.initials: J
authors.lastname: Hua
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000942:Antigens, Bacterial / Q000378:metabolism*; D017209:Apoptosis; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism*; D016481:Helicobacter Infections / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology; D016480:Helicobacter pylori / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015854:Up-Regulation; D014774:Virulence
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C; C080866:cagA protein, Helicobacter pylori; D050760:Cyclin-Dependent Kinase Inhibitor p27