Regulation of invasion and migration by PKCK2 in Helicobacter pylori infected gastric cancer cells

Abstract

Chronic infection with Helicobacter pylori (H. pylori) is causally linked with gastric inflammation and carcinogenesis. Virulent H. pylori strains harbor cag pathogenicity island (PAI) for delivery of the bacterial CagA into gastric epithelial cells. Induction of high motility and an elongated phenotype is considered to be CagA-dependent process. Epithelial-mesenchymal transition (EMT) is a complex cellular program involved in both development and cancer, and the induction of cell migration and invasion is the hallmark of the EMT. Protein kinase casein kinase 2 (PKCK2) plays a critical role in carcinogenesis through signaling pathways related to the epithelial mesenchymal transition (EMT). This study was aimed to investigate the effect of H. pylori infection on the PKCK2 mediated migration and invasion in gastric cancer cells. In in-vivo results, PKCK2α immunostaining revealed strong expression in H. pylori-infected gastric cancer tissues and nuclear expression of PKCK2β was decreased in H. pylori-infected gastric cancer tissues. In in vitro data, H. pylori infection increases host cell PKCK2 activity and decreases PKCK2β expression. Inhibition of PKCK2 with the chemical inhibitor 4,5,6,7-tetrabromo-2-azabenzimidazole (TBB), siRNA or shRNA significantly decreased both invasion / migration and dissociation of the membranous α/β-catenin complex in H. pylori infected gastric cancer cells. These results suggest that H. pylori induces PKCK2-mediated cell migration and invasion through α/β-catenin dissociation in gastric cancer cells