Helicobacter pylori CagA upregulation of CIP2A is dependent on the Src and MEK/ERK pathways.
Helicobacter pylori is classified as a class I carcinogenic factor and its persistent colonization in the stomach induces gastric cancer. Cancerous Inhibitor of PP2A (CIP2A) is a newly identified oncoprotein overexpressed in gastric cancer. Serving as a key oncoprotein, CIP2A also participates in regulation of senescence and proliferation of gastric cells. The combination of aberrant CIP2A expression inducing unlimited cell proliferation, and H. pylori infection eliciting aberrant expression of some key proteins, results in the onset of gastric tumorigenesis. However, the relationship between H. pylori infection and CIP2A expression still remains undefined. The aim of our study was to verify the effect of H. pylori infection on CIP2A expression levels and identify H. pylori signalling molecules and corresponding pathways influencing CIP2A expression. Following plasmid-mediated expression of CagA in human gastric cell lines, the cells were infected with H. pylori and CIP2A expression levels were examined by immunoblotting. Signal inhibitors were used to verify which signal pathways were involved. We also performed CIP2A depletion and H. pylori infection after depletion in AGS cells. H. pylori infection-induced CIP2A expression was dependent on cagA gene expression and CagA phosphorylation. Bacterial oncoprotein CagA upregulated CIP2A expression and this upregulation effect was dependent on Src and Ras/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathways. H. pylori infection-induced Myc stabilization was partially attenuated by CIP2A depletion. The results of our study provide further information for understanding the mechanism of H. pylori carcinogenesis.
Zhao
Dapeng
D
Department of Microbiology and Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
Liu
Zhifang
Z
Department of Biochemistry, School of Medicine, Shandong University, Jinan, PR China.
Ding
Jian
J
Department of Microbiology and Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
Li
Wenjuan
W
Department of Microbiology and Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
Sun
Yundong
Y
Department of Microbiology and Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
Yu
Han
H
Department of Microbiology and Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
Zhou
Yabin
Y
Department of Microbiology and Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
Zeng
Jiping
J
Department of Biochemistry, School of Medicine, Shandong University, Jinan, PR China.
Chen
Chunyan
C
Department of Microbiology and Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
Jia
Jihui
J
Department of Microbiology and Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
D000942:Antigens, Bacterial / Q000378:metabolism*; D001324:Autoantigens / Q000096:biosynthesis*; D001426:Bacterial Proteins / Q000378:metabolism*; D002460:Cell Line; D004847:Epithelial Cells / Q000382:microbiology; D016480:Helicobacter pylori / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D015151:Immunoblotting / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000096:biosynthesis*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction; D015854:Up-Regulation
D000942:Antigens, Bacterial; D001324:Autoantigens; D001426:Bacterial Proteins; C500266:CIP2A protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C080866:cagA protein, Helicobacter pylori; D020929:Mitogen-Activated Protein Kinase Kinases