Helicobacter pylori Induces Cell Migration and Invasion Through Casein Kinase 2 in Gastric Epithelial Cells

Background Chronic infection with H elicobacter pylori ( H . pylori ) is causally linked with gastric carcinogenesis. Virulent H . pylori strains deliver bacterial CagA into gastric epithelial cells. Induction of high motility and an elongated phenotype is considered to be CagA‐dependent process. Casein kinase 2 plays a critical role in carcinogenesis through signaling pathways related to the epithelial mesenchymal transition. This study was aimed to investigate the effect of H . pylori infection on the casein kinase 2‐mediated migration and invasion in gastric epithelial cells. Materials and Methods AGS or MKN 28 cells as human gastric epithelial cells and H . pylori strains Hp60190 (ATCC 49503, CagA + ) and Hp8822 (CagA − ) were used. Cells were infected with H . pylori at multiplicity of infection of 100 : 1 for various times. We measured in vitro kinase assay to examine casein kinase 2 activity and performed immunofluorescent staining to observe E ‐cadherin complex. We also examined β‐catenin transactivation through promoter assay and MMP 7 expression by real‐time PCR and ELISA . Results H . pylori upregulates casein kinase 2 activity and inhibition of casein kinase 2 in H . pylori‐ infected cells profoundly suppressed cell invasiveness and motility. We confirmed that casein kinase 2 mediates membranous α‐catenin depletion through dissociation of the α‐/β‐catenin complex in H . pylori‐ infected cells. We also found that H . pylori induces β‐catenin nuclear translocation and increases MMP 7 expressions mediated through casein kinase 2. Conclusions We show for the first time that CagA + H . pylori upregulates cellular invasiveness and motility through casein kinase 2. The demonstration of a mechanistic interplay between H . pylori and casein kinase 2 provides important insights into the role of CagA + H . pylori in the gastric cancer invasion and metastasis.