CagA–ASPP2 complex mediates loss of cell polarity and favors <i>H. pylori</i> colonization of human gastric organoids
Ludovico Buti, Carlos Ruiz‐Puig, Dennis Sangberg, T.M. Leissing, R. Camille Brewer, Richard Owen, Bruno Sgromo, Christophe Royer, Daniel Ebner, Xin Lü
Abstract
Significance Infection by the bacterium Helicobacter pylori is the main risk factor for stomach cancer. Strains of H. pylori that produce the virulence factor CagA substantially increase stomach cancer risk compared with strains without CagA. CagA disrupts cell polarity—the specialized asymmetric organization within cells—but the mechanism it uses and its influence on colonization are not fully understood. Using a three-dimensional culture of stomach cells (human gastric organoids) and cell lines, we find that the tumor suppressor ASPP2 is crucial in disruption of cell polarity by CagA during H. pylori infection. Interfering with the CagA–ASPP2 interaction, using small molecules or a specific peptide, blocks loss of cell polarity and reduces bacterial colonization in organoids.