| Project/Area Number |
17K08634
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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 | Fukushima Medical University (2019)
Kobe University (2017-2018) |
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Principal Investigator |
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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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 非小細胞肺がん / Ror1受容体型チロシンキナーゼ / Rif低分子量Gタンパク質 / フィロポディア / がん細胞浸潤 / がん浸潤 / Wnt / Rhoファミリー / 低分子量Gタンパク質 / がん細胞増殖 / 癌 / シグナル伝達 |
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| Outline of Final Research Achievements |
We studied the role of Ror1 in invasive properties of non-small cell lung cancer (NSCLC) cells. We have shown that, in PC-9 NSCLC cells, Ror1 induces formation of polarized filopodia through the Rho-family small GTPase, Rif, in 3D-Matrigel. These filopodia were spacially associated with degradation of Matrigel. Suppressed expression of Ror1 or Rif inhibited both filopodia formation and Matrigel degradation. We have also shown that PC-9 cells express high levels of Wnt5a, leading to constitutively activated Wnt5a-Ror1-Dvl signaling, which is required for their invasiveness. Furthermore, SmgGDS was identified as a Rif-binding partner that promotes Rif-induced filopodia formation and invasion in PC-9 cells. Taken together, these results suggest that Wnt5a-Ror1 signaling mediated by SmgGDS and Rif regulates filopodia formation to promote invasion of NSCLC cells.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究によってRor1、Rif、SmgGDSを介した新たなフィロポディア形成機構が見いだされたことは、細胞生物学的知見として重要ある。また、がん細胞浸潤におけるフィロポディアの役割を見いだしたことは、社会的にも意義が多きい。特に、肺がんは本邦におけるがんによる死亡原因の１位であり、中でも肺がんの８割を占める非小細胞肺がんでは、化学療法や放射線治療が有効でないことが治療の大きな障害になっていることから、本研究成果は、有効な治療方法を開発する上でも重要な知見である。
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