Development of novel inhibitor of tumor angiogenesis focusing on CUL3-dependent cholesterol transport

• Project/Area Number: 17K09390
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Nagoya City University
• Principal Investigator: Shikano Michiko 名古屋市立大学, 医薬学総合研究院(医学), 研究員 (70405190)
• 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) ; 城 卓志 名古屋市立大学, 医薬学総合研究院(医学), 名誉教授 (30231369)
• Project Period (FY): 2017-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 大腸癌 / 血管新生 / コレステロール / Cullin-3 / BTBP / 大腸がん / CUL3 / 抗腫瘍血管新生

Outline of Final Research Achievements

To expand the repertories of anti-angiogenic inhibitors, we focused on intracellular trafficking of cholesterol in endothelial cells. In this research project, we found that cullin-3 (CUL3)/BTBP/substrates axes were essential for proper distribution of cholesterol in endothelial cells as well as angiogenesis. Our results suggest the possibility of the protein complex as a promising target for the development of new anti-angiogenic inhibitors.

Academic Significance and Societal Importance of the Research Achievements

本研究で見出したユビキチンリガーゼ複合体依存的な細胞内コレステロール局在制御は今まで無い新しい血管新生阻害剤のシーズ開発標的として強く期待される。コレステロールの可視化技術の発展と相乗的に研究開発が進展していくと思われる。