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2018 Fiscal Year Final Research Report

Functional relationship between Helicobacter pylori CagA and Epstein-Barr virus in gastric carcinogenesis

Research Project

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Project/Area Number 16K08773
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Bacteriology (including mycology)
Research InstitutionThe University of Tokyo

Principal Investigator

Kamiya Naoko  東京大学, 大学院医学系研究科(医学部), 講師 (40279352)

Research Collaborator Seto Yasuyuki  
Project Period (FY) 2016-04-01 – 2019-03-31
Keywordsピロリ菌 / CagA / EBウイルス / 胃がん
Outline of Final Research Achievements

In Japan, most gastric cancers are associated with chronic infection of the stomach mucosa with Helicobacter pylori cagA-positive strains. Approximately 10% of cancers also have Epstein-Barr virus (EBV) in the cancer cells. CagA protein undergoes tyrosine phosphorylation in gastric epithelial cells. Tyrosine-phosphorylated CagA binds to the pro-oncogenic phosphatase SHP2 and thereby deregulates the phosphatase activity, which has been considered to play an important role in gastric carcinogenesis. In this study, we found that the SHP2 homologue SHP1 dephosphorylates CagA. Infection of gastric epithelial cells with EBV induced SHP1 promoter hypermethylation, which strengthened phosphorylation-dependent CagA action via epigeneticc downregulation of SHP1 expression.

Free Research Field

感染腫瘍学

Academic Significance and Societal Importance of the Research Achievements

ピロリ菌の病原因子であるCagAタンパク質は、胃上皮細胞内でチロシンリン酸化されて発がん活性を発揮する。本研究では、CagAをチロシン脱リン酸化する酵素としてSHP1を同定した。SHP1は胃がん抑制酵素として位置づけられることから、本研究成果の医学的意義は極めて大きい。さらに、Epstein-Barrウイルスとピロリ菌が重感染した細胞では、EBウイルス感染によりSHP1発現が低下する結果、ピロリ菌CagAの発がん活性が増強することを明らかにした。発がんにおける細菌とウイルスの連携作用を世界で初めて示した研究成果である。

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Published: 2020-03-30  

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