Autophagy induced byHelicobacter pyloriinfection is necessary for gastric cancer stem cell emergence

Background The main cause of gastric cancer is the infection by the bacteriumHelicobacter pyloriwhich induces a chronic inflammation and an epithelial-to-mesenchymal transition (EMT) leading to the emergence of cells with cancer stem cell (CSC) properties. However, the underlying mechanisms have not been fully characterized. Moreover,H. pylorimodulates the host cell autophagic process, but a few studies have investigated the role of this process in tumoral transformation. The aim of this study was to determine whetherH. pylori-induced autophagy has a role in CSC emergence. Methods Autophagic flux in response toH. pyloriinfection was characterized in AGS cell line expressing the tandem-tagged mCherry-GFP-LC3 protein and using a ratiometric flow cytometry analysis. Then, AGS and MKN45 cell lines were treated with bafilomycin or chloroquine, two pharmaceutical well-known inhibitors of autophagy, and different EMT and CSC characteristics were analyzed. Results First, a co-expression of the gastric CSC marker CD44 and the autophagic marker LC3 in mice and human stomach tissues infected withH. pyloriwas observed. Then, we demonstrated in vitro thatH. pyloriwas able to activate the autophagy process with a reduced autophagic flux. Finally, infected cells were treated with autophagy inhibitors, which reduced (i) appearance of mesenchymal phenotypes and migration ability related to EMT and (ii) CD44 expression as well as tumorsphere formation capacities reflecting CSC properties. Conclusion In conclusion, all these data show thatH. pylori-induced autophagy is implicated in gastric CSC emergence and could represent an interesting therapeutic target.

Automated summary

The infection of Helicobacter pylori can induce autophagy, which in turn affects the formation of gastric cancer stem cells. Inhibiting autophagy may be a potential therapeutic target for gastric cancer.