CDK1 bridges NF-?B and 0-catenin signaling in response to H. pylori infection in gastric tumorigenesis

Infection with Helicobacter pylori (H. pylori) is the main risk factor for gastric cancer, a leading cause of cancer-related death worldwide. The oncogenic functions of cyclin-dependent kinase 1 (CDK1) are not fully understood in gastric tumorigenesis. Using public datasets, quantitative real-time PCR, western blot, and immunohistochemical (IHC) analyses, we detect high levels of CDK1 in human and mouse gastric tumors. H. pylori infection induces activation of nuclear factor kB (NF-kappa B) with a significant increase in CDK1 in in vitro and in vivo models (p < 0.01). We confirm active NF-kappa B binding sites on the CDK1 promoter sequence. CDK1 phosphorylates and inhibits GSK-30 activity through direct binding with subsequent accumulation and activation of 0-catenin. CDK1 silencing or pharmacologic inhibition reverses these effects and impairs tumor organoids and spheroid formation. IHC analysis demonstrates a positive correlation between CDK1 and 0-catenin. The results demonstrate a mechanistic link between infection, inflammation, and gastric tumori-genesis where CDK1 plays a critical role.