| Project/Area Number |
18K07242
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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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| Review Section |
Basic Section 50010:Tumor biology-related
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| Research Institution | Kitasato University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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)
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| Keywords | 神経芽腫 / Src / パキシリン / p130Cas / dasatinib / Srcファミリーキナーゼ / 細胞運動能 / 細胞増殖能 / キナーゼ阻害剤 / Srcキナーゼ / RNAi / チロシンリン酸化 / キナーゼ阻害薬 / Alk / チロシンキナーゼ |
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| Outline of Final Research Achievements |
SFKs are known to be activated in various types of cancers and involved especially in the progression of the disease. The objective of this study is to elucidate the role of SFKs and their substrates in the progression of neuroblastoma. SFK inhibitors such as saracatinib, bosutinib and dasatinib generally caused more significant suppressive effects in cell migration than in cell proliferation in NB39-nu cells. Among SFK inhibitors, dasatinib showed outstanding inhibition of cell migration at the concentration as low as 10 nM. At this concentration, dasatinib caused inhibition of the phosphorylation of several substrates of SFKs such as paxillin and p130Cas. On the other hand, siRNA inhibition of these substrates did not show significant effect on the migration of NB39-nu.
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| Academic Significance and Societal Importance of the Research Achievements |
神経芽腫は小児腫瘍の一つとしてがん遺伝子の活性化を引き起こす変異に乏しいにも関わらず高頻度で転移が見られ、また一方で1歳未満で発症する例では自然退縮を起こす症例があることから、転移に関わるチロシンキナーゼであるSrcファミリーの可逆的な活性化が関わっていることを考えている。Src阻害剤は神経芽腫の運動能や浸潤能を選択的に阻害し、増殖能に対する影響は限定的であることから、神経芽腫においても転移などの悪性化に関わる性質にSrcファミリーキナーゼが関わることが示唆された。将来的に進行した神経芽腫に対する適切なSrc阻害剤が有効である可能性が示された。
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