Elucidation of mechanisms underlying angiogenesis is important for the development of new anti-angiogenic drugs

Research Project

Project/Area Number	18K08013
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 53010:Gastroenterology-related
Research Institution	Nagoya City University
Principal Investigator	Hayashi Noriyuki 名古屋市立大学, 医薬学総合研究院(医学), 研究員 (60745404)
Co-Investigator(Kenkyū-buntansha)	前川大志愛媛大学, プロテオサイエンスセンター, 講師 (10771917) 田中守名古屋市立大学, 医薬学総合研究院(医学), 助教 (80617861) 片岡洋望名古屋市立大学, 医薬学総合研究院(医学), 教授 (40381785)
Project Period (FY)	2018-04-01 – 2021-03-31
Project Status	Completed (Fiscal Year 2020)
Budget Amount *help	¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000) Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords	血管新生 / ユビキチンリガーゼ / 翻訳制御 / 血管新生能 / CUL3/KCTD10 / microRNA / CUL3 / KCTD10
Outline of Final Research Achievements	Elucidation of mechanisms underlying angiogenesis is important for the development of new anti-angiogenic drugs. Here, we found that EIF3D, a critical translational factor, is ubiquitinated by the cullin-3 (CUL3)/KCTD10 ubiquitin ligase complex in both endothelial cells and hepatocellular carcinoma cells. Knockdown of EIF3D in endothelial cells drastically inhibited tube formation of endothelial cells, that mimics angiogenesis in vitro. Our results suggest that CUL3/KCTD10/EIF3D would be a promising target for development of novel anti-angiogenic drugs.
Academic Significance and Societal Importance of the Research Achievements	現在、臨床応用されている血管新生阻害剤は全て血管内皮細胞増殖因子 (VEGF)または、VEGF受容体を標的としている。より効果的な癌治療を進めるためには、血管新生阻害剤のレパートリーを拡充する必要がある。今後、本研究で明らかにしたCUL3/KCTD10/EIF3D複合体を標的とした新しい血管新生阻害剤の開発が期待される。