2018 Fiscal Year Final Research Report
Molecular Mechanisms of Tumorigenesis, Invasion, and Metastasis by the Small GTPase Ral
| Project/Area Number |
16K08574
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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 |
General medical chemistry
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | Ral / RalGAP / Ras / 口腔扁平上皮がん / 膵臓がん |
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| Outline of Final Research Achievements |
In this study, we analyzed the molecular mechanisms of oncogenesis by activation of the small GTPase Ral. Constitutive activation of Ral by the reduction of RalGAP expression is involved in promoting the migration and invasion of oral squamous cell carcinoma cells and pancreatic cancer cells. In addition, expression of RalGAPα2 is reduced in oral cancer tissue, possibly due to DNA and histone modifications in the promoter region of RalGAPα2 gene.
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| Free Research Field |
生化学
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| Academic Significance and Societal Importance of the Research Achievements |
Rasファミリーの低分子量Gタンパク質Ralは、多くのがんで活性化されており、その阻害剤が開発される（Yan et al. Nature, 2014）など非常に注目されている。本研究ではRalの抑制性調節因子であるRalGAPの発現が、がんにおいて転写レベルで低下しており、それがRalの高度な活性化につながることを示した。Ralの機能制御機構の理解は新しいタイプの抗がん薬の開発につながる可能性がある。
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