| Project/Area Number |
17K11282
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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 |
Obstetrics and gynecology
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| Research Institution | Kyushu University |
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Principal Investigator |
Yagi Hiroshi 九州大学, 医学研究院, 助教 (70623552)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | GPCR / シグナル伝達 / 卵巣癌 / 上皮間葉転換 / Gタンパク / EMT / 癌 / 転移 |
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| Outline of Final Research Achievements |
G-protein-coupled receptor (GPCRs) are seven transmembrane receptors, and form a largest family among cell surface molecules. GPCR signaling regulates diverse biological functions, and is involved in cancer progression. GPCRs signal through the activation of heterotrimeric G proteins. Among them, we have focused on the role of Ga13 in the progerssion of human ovarian cancer. Ga13 is highly expressed in human ovarian cancer tissues. In vitro study revealed that the activation of Ga13 induces epithelial-mesenchymal transition in ovarian cancer cells through down-regulation of LATS1, a critical component of the Hippo signalling pathway. Our findings uncover novel mechanisms through which Ga13 activation induces dysregulation of the Hippo signalling pathway, leading to aggressive cancer phenotypes, thereby identifying a potential target for preventing metastatic spread of ovarian cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
現在の治療薬の約35%がGPCRを標的としているが、それらの治療薬が標的としているのは、GPCR全体の約15%に過ぎない。また、ヒト癌組織で発現を認めるGPCRのうち140種以上についてはリガンド分子やその機能が不明であり、興味深いことにそれらの多くはGa13とcouplingすることが報告されている。シグナル選択的なGPCRアンタゴニストや、GPCRシグナルを間接的に阻害するアロステリックタンパクなど、新たなコンセプトに基づく治療薬が開発されつつある現状を考慮すると、本研究の成果が癌に対する新たな治療法の開発につながることが期待でき、社会的意義は大きいものと考えられる。
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