2016 Fiscal Year Final Research Report
Autophagy and metabolic regulation by multiple transcription factors
| Project/Area Number |
26253019
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Niigata University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
WAGURI Satoshi 福島県立医科大学, 医学部, 教授 (30244908)
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| Research Collaborator |
MIZUSHIMA Tsunehiro
SOGA Tomoyoshi
OKABE Takayoshi
NAGANO Tetsuo
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | タンパク質分解 / オートファジー / p62 / Nbr1 / Metabolism |
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| Outline of Final Research Achievements |
In this research project, we reveal the molecular mechanism of p62/Sqstm1-dependent malignant progression, and suggest that molecular targeting of p62/Sqstm1 represents a potential chemotherapeutic approach against hepatocellular carcinoma (HCC). Phosphorylation of p62/Sqstm1 at Ser349 directs glucose to the glucuronate pathway, and glutamine toward glutathione synthesis through activation of the transcription factor Nrf2. These changes provide HCC cells with tolerance to anti-cancer drugs and proliferation potency. Phosphorylated p62/Sqstm1 accumulates in tumor regions positive for hepatitis C virus (HCV). An inhibitor of phosphorylated p62-dependent Nrf2 activation suppresses the proliferation and anticancer agent tolerance of HCC. Our data indicate that this Nrf2 inhibitor could be used to make cancer cells less resistant to anticancer drugs, especially in HCV-positive HCC patients.
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| Free Research Field |
分子細胞生物学
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