2015 Fiscal Year Final Research Report
Host cell characteristics involved in gastric carcinogenesis by H. pylori infection
| Project/Area Number |
25460173
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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 |
Environmental and hygienic pharmacy
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| Research Institution | Keio University |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | オートファジー / がん蛋白質 / ピロリ菌 / CD44 / VacA / CagA |
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| Outline of Final Research Achievements |
Intracellular CagA is degraded by autophagy. CagA-degradin autophagy was suppressed in CD44v9-expressing host cells, resulting in the specific accumulation of CagA in these cells. This autophagic pathway was activated by VacA via binding to LRP1. During autophagy, LRP1 was translocated to the nuclei, and increased the LAMP1 expression via binding to the lamp1 promoter. Specific knockdown of lamp1 decreased the formation of autophagolysosome, leading to the intracellular accumulation of CagA. Additionally, we identified a LRP1-binding protein which binds to LRP1 in the nuclei and suppresses transcription of LAMP1. In cells overexpressing the LRP1-binding protein, autophagy was suppressed and then CagA accumulated. The accumulation of CagA in LRP1-binding protein overexpressing cells caused increased CD44v9 expressions. The expression levels of the LRP1-binding protein determine the intracellular CagA stability associated with the induction of CD44v9 expression.
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| Free Research Field |
細菌学
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