| Project/Area Number |
26861332
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Kyushu University |
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Principal Investigator |
Hiroshi Yagi 九州大学, 医学(系)研究科(研究院), 助教 (70623552)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | GPCR / 卵巣癌 / シグナル伝達 / Rho / 転移 / 細胞増殖 |
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| Outline of Final Research Achievements |
Cancer cells can co-opt the activity of G protein coupled receptors (GPCRs) signaling. Recent analyses revealed that not only GPCRs or its ligands, but also heterotrimeric G proteins play critical roles in cancer progression. Among G proteins, we have focused on G12/13. In immunohistochemical analysis, G12/13 is highly expressed in ovarian cancer tissues. Increased expression of G13 promotes cell proliferation in vitro and tumor grwoth in vivo. To further examine underlying mechanisms of G13-regulated cell proliferation, we took advantage of synthetic biology approach using mutant GPCR and G protein. Detailed analysis revealed that the activation of G13 induces dephosphorylation and nuclear translocation of YAP, which is a core component of Hippo pathway. In addition, inhibition of YAP activity by shRNA or specific inhibitor blocked proliferation of ovarian cancer cells. These data represents G13-YAP signaling axis as a novel therapeutic target of ovarian cancer.
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