Professor Masanori Hatakeyama of the University of Tokyo Graduate School of Medicine and colleagues have found that protein phosphatase (SHP1) is an enzyme that suppresses the carcinogenic activity of the protein CagA produced by Helicobacter pylori.Furthermore, we found that the expression of SHP1 was suppressed in the cells of the stomach infected with Epstein-Barr (EB) virus, and the carcinogenic activity of the Helicobacter pylori CagA protein was enhanced.This result is the first in the world to clarify the mechanism by which bacteria and viruses work together to promote the development of cancer in humans.This research is a collaboration with researchers from the Graduate School of Medicine, Chiba University and the Graduate School of Medicine, the University of Tokyo.
Helicobacter pylori is said to increase the risk of developing gastric cancer, and it has been reported that almost all H. pylori detected in Japan are CagA-positive H. pylori, which produces the protein CagA.CagA injected into gastric cells by Pyrroli bacteria is tyrosine-phosphorylated by phosphorylating enzymes (Src family kinase and Abl kinase), and then binds to tyrosine dephosphorylating enzyme (phosphatase) SHP2 to promote the development of gastric cancer. increase. Dephosphorylation of CagA is important in suppressing canceration, but SHP2 does not have the ability to dephosphorylate CagA.
We have now identified SHP2, a sibling of SHP1, as an enzyme that dephosphorylates the Helicobacter pylori protein CagA. As a result of tyrosine dephosphorylation by SHP1, the carcinogenic activity of the CagA protein was neutralized, suggesting that SHP1 is a molecule that suppresses the development of gastric cancer.On the other hand, EB virus infection to cancer cells is known in about 10% of gastric cancer cases, and as a result of this co-infection, the site called the promoter of the SHP1 gene is highly methylated, and as a result, the expression of SHP1 is suppressed. It was found that the carcinogenic activity of the Helicobacter pylori CagA protein was enhanced.It is the first time in the world to elucidate the link between carcinogenic bacteria and carcinogenic viruses in the development of human cancer.
