Role of novel ghrelin receptor binding protein PLA2G16 in gastrointestinal cancer cells

• Project/Area Number: 17K09344
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Hokkaido University
• Principal Investigator: Takeda Hiroshi 北海道大学, 薬学研究院, 教授 (60261294)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: グレリン受容体 / 消化器癌 / PLA2G16

Outline of Final Research Achievements

To clarify the significance of the ghrelin receptor (GHS-R1a) expressed in gastrointestinal cancer cells, we searched for intracellular molecules that interact with GHS-R1a by the yeast two-hybrid method. As a result, I found that PLA2G16 (HRASLS3 / HRSL3 / HREV107 H-Rev107 /AdPLA), which has been reported as a molecule that negatively regulates Ras function, binds to the C-terminal part of GHS-R1a. Furthermore, it was revealed that GHS-R1a suppresses phospholipase A2 activity of PLA2G16. It is suggested that GHS-R1a may influence the function of gastrointestinal cancer cells via regulation of PLA2G16.

Academic Significance and Societal Importance of the Research Achievements

本研究は、これまで不明確であった消化器癌細胞におけるグレリン受容体の機能制御を明らかにし たものである。本研究をさらに展開することにより、グレリンによる癌増殖経路を細胞選択的に遮断する方法を 見出すことが期待できる。また、グレリン受容体作動薬を臨床応用する際、これまで懸念されてきたような癌細胞増殖への影響を排除して、このクラスの薬剤を臨床現場で安全に使用できる理論的基盤を構築できる可能性がある。

Research Products

• [Journal Article] Metformin Regulates the Expression of CD133 Through the AMPK-CEBPβ Pathway in Hepatocellular Carcinoma Cell Lines (2019)
  • Author(s): Maehara Osamu、Ohnishi Shunsuke、Asano Ayaka、Suda Goki、Natsuizaka Mitsuteru、Nakagawa Koji、Kobayashi Masanobu、Sakamoto Naoya、Takeda Hiroshi
  • Journal Title: Neoplasia Volume: 21 Issue: 6 Pages: 545-556
  • DOI: 10.1016/j.neo.2019.03.007
  • Peer Reviewed / Open Access
• [Journal Article] Psychological stress in aged female mice causes acute hypophagia independent of central serotonin 2C receptor activation. (2017)
  • Author(s): Matsumoto C, Yamada C, Sadakane C, Nahata M, Hattori T, Takeda H.
  • Journal Title: PLoS One. Volume: 12 Issue: 11 Pages: e0187937-e0187937
  • DOI: 10.1371/journal.pone.0187937
  • NAID: 120006369342
  • Peer Reviewed / Open Access
• [Presentation] Dysregulation of liver mitochondrial function and dynamics is associated with vulnerability to undernutrition in aged mice. (2019)
  • Author(s): Nahata M., Sekine H., Mogami S., Iizuka S., Fujitsuka N., Takeda H.
  • Organizer: DDW2019
  • Int'l Joint Research
• [Presentation] Dysfunction of starvation-induced liver autophagy is associated with disruption of adaptive energy metabolism and increased mortality in aged mice on restricted diet. (2017)
  • Author(s): Iizuka S, Nahata M, Sekine H, Fujitsuka N, Ohbuchi K, Komokata N, Shimobori C, Hattori T, Takeda H.
  • Organizer: Digestive Disease Week 2017
  • Int'l Joint Research
• [Presentation] Gender difference in anorexia following stress exposure is dependent on the blocking of ghrelin signal in the NTS. (2017)
  • Author(s): Yamada C, Iizuka S, Saegusa Y, Hattori T, Takeda H.
  • Organizer: Digestive Disease Week 2017
  • Int'l Joint Research