Development of novel anti-angiogenic drugs for effective colorectal cancer treatment

• Project/Area Number: 18K16317
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Ehime University
• Principal Investigator: Tanigawa Kazufumi 愛媛大学, 医学部附属病院, 助教(病院教員) (20527519)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: SNX9 / 血管新生 / 大腸癌 / 腫瘍血管新生 / 大腸がん / 抗血管新生薬 / ユビキチンE3リガーゼタンパク質

Outline of Final Research Achievements

Angiogenesis is extremely active in the colorectal cancers, and thus angiogenic inhibitors exhibit good anti-tumor efficacy in colorectal cancer therapy. In this study, we aim to identify novel molecular machinery for angiogenesis, which would be a promising target for the development of new anti-angiogenic inhibitors. We found that SNX9 is essential for angiogenesis partially through the recycling of integrin beta 1 in human endothelial cells. The protein expression of SNX9 was increased in tumor endothelium of human colorectal cancer tumors. We also established the AlphaScreen system for the screen of agents that inhibit the molecular functions of SNX9 in vitro.

Academic Significance and Societal Importance of the Research Achievements

本研究は、SNX9の血管新生における機能を細胞生物学及び、臨床組織学の観点から解明した点で学術的意義は高い。また、SNX9の機能を人為的に阻害する血管新生阻害剤のシーズ探索のためのスクリーニング系を構築した点で、創薬応用への展開が期待できる。

Research Products

• [Journal Article] SNX9 determines the surface levels of integrin β1 in vascular endothelial cells: Implication in poor prognosis of human colorectal cancers overexpressing SNX9. (2019)
  • Author(s): Tanigawa K, Maekawa M, Kiyoi T, Nakayama J, Kitazawa R, Kitazawa S, Semba K, Taguchi T, Akita S, Yoshida M, Ishimaru K, Watanabe Y, Higashiyama S.
  • Journal Title: J Cell Physiol. Volume: in press Issue: 10 Pages: 17280-17294
  • DOI: 10.1002/jcp.28346
  • Peer Reviewed / Open Access
• [Presentation] 大腸癌組織に高発現する新規血管新生制御因子SNX9の機能解析 (2019)
  • Author(s): 谷川和史、前川大志、清井武志、中山淳、北澤理子、北澤荘平、仙波憲太郎、田口友彦、渡部祐司、東山繁樹
  • Organizer: 第60回日本生化学会中国・四国支部会例会
• [Presentation] 新規に同定した血管新生因子SNX9は大腸癌組織に高発現する (2019)
  • Author(s): 谷川和史、前川大志、清井武志、北澤理子、北澤荘平、秋田聡、吉田素平、石丸啓、渡部祐司、東山繁樹
  • Organizer: 第74回日本消化器外科学会総会