The main risk factor for stomach cancer is an infection by Helicobacter pylori (H. pylori). Strains of H. pylori that produce the toxin CagA significantly increase the risk of stomach cancer compared with strains that do not. In a January paper in the Proceedings of the National Academy of Sciences, Ludwig Oxford’s Xin Lu and colleagues found that interaction between the tumor suppressor ASPP2 and CagA is a key event in disruption of cell polarity—the asymmetric organization of cells—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, which are tiny, self-organized three-dimensional tissue cultures derived from stem cells, in this case from the stomach. The results suggest that agents that can prevent changes in host-cell polarity upon bacterial infection might represent a new class of antimicrobial agents.
This article appeared in the April 2020 issue of Ludwig Link. Click here to download a PDF (1 MB).