Functional relationship between Helicobacter pylori CagA and Epstein-Barr virus in gastric carcinogenesis
| Project/Area Number |
16K08773
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Bacteriology (including mycology)
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Kamiya Naoko 東京大学, 大学院医学系研究科(医学部), 講師 (40279352)
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| Research Collaborator |
Seto Yasuyuki
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | ピロリ菌 / CagA / EBウイルス / 胃がん / Epstein-Barrウイルス / ヘリコバクター・ピロリ / Epstein-Barr ウイルス / 癌 / 感染症 / 細菌 / ウィルス |
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| 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.
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| 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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Report
(4 results)
Research Products
(7 results)
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[Journal Article] Enhanced expression of PKM2 is involved in the gastric cancer development via regulating cancer specific metabolism.2017
Author(s)
Shiroki T, Yokoyama M, Tanuma N, Maejima R, Tamai K, Yamaguchi K, Oikawa T, Noguchi T, Miura K, Fujiya T, Shima H, Sato I, Kamiya N, Hatakeyama M, Iijima K, Shimosegawa T and Satoh K.
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Journal Title
Cancer Sci
Volume: 印刷中
Pages: 931-940
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] CEACAM6 is upregulated by Helicobacter pylori CagA and is a biomarker for early gastric cancer.2016
Author(s)
Roy, R.K., Hoppe, M.M., Sharma, N., Srivastava, S., Tan, K.T., Yang, H., Voon, D.C., Pang, B., The, M., Murata-Kamiya, N., Hatakeyama, M., Samanta, A., Chang, Y.T., Ito, Y., Ho, K.Y., Tan, P., Soong, R., Koeffler, P.H., Yeoh, K.G. and Jeyasekharan, A.D.
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Journal Title
Oncotarget
Volume: 7
Pages: 55290-55301
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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