title: H. pylori CagL-Y58/E59 prime higher integrin α5β1 in adverse pH condition to enhance hypochlorhydria vicious cycle for gastric carcinogenesis.
abstract: OBJECTIVE
  H. pylori CagL amino acid polymorphisms such as Y58/E59 can increase integrin α5β1 expression and gastric cancer risk. Hypochlorhydria during chronic H. pylori infection promotes gastric carcinogenesis. The study test whether CagL-Y58/E59 isolates may regulate integrin α5β1 to translocate CagA via the type IV secretory system even under adverse pH conditions, and whether the integrin α5β1 expression primed by H. pylori is a pH-dependent process involving hypochlorhydria in a vicious cycle to promote gastric carcinogenesis.
  
  
  METHODS
  The expressions of integrin α5 and β1, CagA phosphorylation, IL-8, FAK, EGFR, and AKT activation of AGS cells exposed to CagL-Y58/E59 H. pylori, isogenic mutants, and different H. pylori CagL amino acid replacement mutants under different pH values were determined. Differences in the pepsinogen I/II ratio (indirectly indicating gastric acidity) and gastric integrin α5β1 expression were compared among the 172 H. pylori-infected patients with different cancer risks.
  
  
  RESULTS
  Even under adversely low pH condition, H. pylori CagL-Y58/E59 still keep active integrin β1 with stronger binding affinity, CagA translocation, IL-8, FAK, EGFR, and AKT activation than the other mutants (p<0.05). The in vitro assay revealed higher priming of integrin α5β1 by H. pylori under elevated pH as hypochlorhydria (p<0.05). In the H. pylori-infected patients, the gastric integrin α5β1 expressions were higher in those with pepsinogen I/II ratio <6 than in those without (p<0.05).
  
  
  CONCLUSIONS
  H. pylori CagL-Y58/E59 prime higher integrin under adverse pH and may involve to enhance hypochlorhydria vicious cycle for gastric carcinogenesis, and thus require an early eradication.
authors.affiliation: Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Yeh
authors.forename: Hsiu-Chi
authors.initials: HC
authors.lastname: Cheng
authors.forename: Hsiao-Bai
authors.initials: HB
authors.lastname: Yang
authors.forename: Wei-Lun
authors.initials: WL
authors.lastname: Chang
authors.forename: Bor-Shyang
authors.initials: BS
authors.lastname: Sheu
mesh_terms: D000126:Achlorhydria / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D016481:Helicobacter Infections / Q000378:metabolism*; D016480:Helicobacter pylori / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D039081:Integrin alpha5beta1 / Q000235:genetics / Q000378:metabolism*; D016209:Interleukin-8 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009154:Mutation; D020116:Pepsinogen A / Q000378:metabolism; D020115:Pepsinogen C / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D021381:Protein Transport; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology
chemical_list: D001426:Bacterial Proteins; D039081:Integrin alpha5beta1; D016209:Interleukin-8; C568315:cagL protein, Helicobacter pylori; D020115:Pepsinogen C; D020116:Pepsinogen A; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt