Helicobacter pylori cytotoxin-associated gene A protein upregulates α-enolase expression via Src/MEK/ERK pathway: implication for progression of gastric cancer.
Persistent infection with Helicobacter pylori confers an increased risk for the development of gastric cancer. In our previous investigations, we found that ENO1 was overexpression in cagA-positive H. pylori-infected gastric epithelial AGS cells by proteomic method, in contrast to the isogenic cagA knock out mutant H. pylori-infected cells. ENO1 is a newly identified oncoprotein overexpressed in some cancer. However, the relationship between H. pylori infection and ENO1 expression still remains undefined. The AGS gastric cancer cells were transfected with WT-cagA plasmid and PR-cagA plasmids. Expression of ENO1 mRNA and protein were measured by real-time quantitative PCR and western blot analysis. Signal protein inhibitor treatment was used to investigate the signal pathways. It was found that the ENO1 mRNA and protein overexpression levels were dependent on cagA gene expression and CagA protein phosphorylation. Further analysis revealed that the Src, MEK and ERK pathway was involved in this upregulation effect. Our data suggest that ENO1 was upregulated by CagA protein through activating the Src and MEK/ERK signal pathways, thereby providing a novel mechanism underlying H. pylori-mediated gastric diseases.
Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, P.R. China.
Shuaiyin
S
Chen
Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, P.R. China.
Guangcai
G
Duan
Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, P.R. China.
Rongguang
R
Zhang
Henan Key Laboratory of Molecular Medicine, Zhengzhou, Henan, P.R. China.
Qingtang
Q
Fan
D000942:Antigens, Bacterial / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D018450:Disease Progression; D016481:Helicobacter Infections / Q000150:complications* / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D010751:Phosphopyruvate Hydratase / Q000096:biosynthesis*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D013274:Stomach Neoplasms / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D015533:Transcriptional Activation; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*; D015854:Up-Regulation; D019061:src-Family Kinases / Q000378:metabolism*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C080866:cagA protein, Helicobacter pylori; D019061:src-Family Kinases; C095157:ENO1 protein, human; D010751:Phosphopyruvate Hydratase