Development of peptides inhibiting tumor angiogenesis and metastasis to develop a novel anti-cancer drug
| Project/Area Number |
18H02601
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 48030:Pharmacology-related
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
船越 祐司 筑波大学, 医学医療系, 助教 (30415286)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2018: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
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| Keywords | 抗癌剤 / 腫瘍血管新生 / 癌細胞浸潤・転移 / ペプチド / 低分子量G蛋白質 / Arf6 / 浸潤・転移 / 低分子量Gタンパク質 / 抗がん剤 / シグナル伝達 / 転移 |
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| Outline of Final Research Achievements |
In this project, we aim to develop an innovative, highly efficient anti-cancer drug, which inhibits both tumor angiogenesis and cancer cell metastasis, by inhibiting the small GTPase Arf6. We propose a novel Arf6-mediated cancer cell invasion mechanism: Arf6 promotes cancer cell invasion by enhancing the recycling of plasma membrane proteins mediated by the deubiquitinating enzyme TRE17. We also developed a low-molecular-weight drug lead peptide with 39 amino acids, which specifically inhibits Arf6 activation. Furthermore, we partially revealed the binding site of Arf6 for the lead peptide by the NMR analysis.
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| Academic Significance and Societal Importance of the Research Achievements |
腫瘍増大に必須な現象である腫瘍血管新生に対する阻害剤が新たな抗癌剤として開発された。しかしながら、腫瘍血管新生が阻害されると癌細胞の転移能が亢進するため、血管新生阻害薬の有効性は限定的である。そのため、腫瘍血管新生と癌細胞転移の両方を同時に抑制できる新規な抗癌剤の開発が望まれる。Arf6は両機能を制御する鍵因子であり、本研究で創生した創薬リードペプチドは、単独で腫瘍血管新生と癌細胞転移を阻害する高い治療効果をもたらすとともに、患者の負担を軽減し、副作用を抑える革新的な癌治療薬となることが期待される。
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Report
(4 results)
Research Products
(14 results)
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[Journal Article] Arf1 and Arf6 Synergistically Maintain Survival of T Cells during Activation2021
Author(s)
M. Sumiyoshi, Y. Kotani, Y. Ikuta, K. Suzue, M. Ozawa, T. Katakai, T. Yamada, T. Abe, K. Bando, S. Koyasu, Y. Kanaho, T. Watanabe and S. Matsuda
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Journal Title
J Immunology
Volume: 206
Pages: 366-375
DOI
Related Report
Peer Reviewed / Open Access
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