<i>Helicobacter pylori</i>induces the expression of Lgr5 and stem cell properties in gastric target cells

Abstract

<i>Helicobacter pylori</i> infection predisposes carriers to a high risk of developing gastric cancer. The cell-of-origin of antral gastric cancer is the Lgr5⁺ stem cell. Here, we show that infection of antrum-derived gastric organoid cells with <i>H. pylori</i> increases the expression of the stem cell marker Lgr5 as determined by immunofluorescence microscopy, qRT-PCR, and Western blotting, both when cells are grown and infected as monolayers and when cells are exposed to <i>H. pylori</i> in 3D structures. <i>H. pylori</i> exposure increases stemness properties as determined by spheroid formation assay. Lgr5 expression and the acquisition of stemness depend on a functional type IV secretion system (T4SS) and at least partly on the T4SS effector CagA. The pharmacological inhibition or genetic ablation of NF-κB reverses the increase in Lgr5 and spheroid formation. Constitutively active Wnt/β-catenin signaling because of <i>Apc</i> inactivation exacerbates <i>H. pylori</i>-induced Lgr5 expression and stemness, both of which persist even after eradication of the infection. The combined data indicate that <i>H. pylori</i> has stemness-inducing properties that depend on its ability to activate NF-κB signaling.