Chronic inflammation contributes to the development of gastric cancer, the second leading cause of cancer-related deaths worldwide. Aurora kinase A (AURKA) is frequently overexpressed in gastrointestinal and other cancers, but its roles in inflammation and tumorigenesis are unclear.
Wael El-Rifai, M.D., Ph.D., professor of Surgery, and colleagues have now linked AURKA overexpression to inflammation. They demonstrated that increased AURKA expression correlates with increased levels of pro-inflammatory molecules (including NF-kappaB) in the gastric mucosa of a mouse model that develops gastric cancer, and in gastric tissue samples from patients with pre-malignant and malignant lesions.
They showed that inhibition of AURKA reduces NF-kappaB activity in gastric cancer cells, reduces xenograft tumor growth, and reverses the development of gastric tumors in the mouse model. They found that AURKA activates NF-kB by directly binding to and modifying the NF-kB regulator, IkB.
The findings, reported in the December issue of Gastroenterology, highlight the importance of AURKA in gastric tumorigenesis and support the potential of AURKA inhibitors as therapeutic agents for gastric cancer.
This research was supported by grants from the National Institutes of Health (CA131225, CA095103, CA068485, DK058404) and from the Department of Veterans Affairs.
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