2021 Fiscal Year Final Research Report
Molecular Mechanism of Tumor Supression by RalGAP and Biguanides
Project/Area Number |
19K07342
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 48040:Medical biochemistry-related
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Research Institution | Tohoku University |
Principal Investigator |
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | Ral / RalGAP / Ras / 膵臓がん / PDAC |
Outline of Final Research Achievements |
Ral is a low molecular weight GTP-binding protein belonging to the Ras family and regulates diverse cellular processes including cell proliferation, membrane traffic, and actin cytoskeleton reorganization. Aberrant activation of Ral is known to promote malignant transformation of cancer. In this study, we found that the constitutive activation of Ral promoted the invasion and metastasis of pancreatic cancer cells. In addition, gene expression analysis identified a cytokine whose expression and secretion increased with Ral activation. These findings reveal the molecular mechanisms downstream of Ral that play a role in invasion and metastasis of pancreatic cancer cells.
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Free Research Field |
生化学
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Academic Significance and Societal Importance of the Research Achievements |
これまでの多くの知見は、Ralの異常な活性化が、がん化、がんの浸潤・転移に重要であることを示している。特に膵臓がんにおいてはRalの活性化が顕著であることが知られる。しかし、がんの悪性化を制御するRal下流の分子メカニズムについてはこれまで不明であった。本研究において膵臓がんの浸潤・転移におけるRalの役割を明らかにした。現在、Ral経路を標的とする抗がん剤の開発が進められており、本成果は膵臓がんに対する新たな治療薬の開発につながりうるものである。
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