Other
13 Authors
- Cao L,
- Hu T,
- Poveda J,
- McDonald OG,
- Khalafi S,
- Chen Z,
- Lu H,
- El-Rifai W,
- Al-Mathkour M,
- Peng D,
- Zaika A,
- Soutto M,
- Zhu S
| First Author | Zhu S | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 1 | Pages | 112005 |
| PubMed ID | 36681899 | Mgi Jnum | J:333435 |
| Mgi Id | MGI:7432239 | Doi | 10.1016/j.celrep.2023.112005 |
| Citation | Zhu S, et al. (2023) CDK1 bridges NF-kappaB and beta-catenin signaling in response to H. pylori infection in gastric tumorigenesis. Cell Rep 42(1):112005 |
| abstractText | 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 kappaB (NF-kappaB) with a significant increase in CDK1 in in vitro and in vivo models (p < 0.01). We confirm active NF-kappaB binding sites on the CDK1 promoter sequence. CDK1 phosphorylates and inhibits GSK-3beta activity through direct binding with subsequent accumulation and activation of beta-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 beta-catenin. The results demonstrate a mechanistic link between infection, inflammation, and gastric tumorigenesis where CDK1 plays a critical role. |
