Study on PRIP roles in cancer cell proliferation and migration

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K11503
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Hiroshima University
• Principal Investigator: Kanematsu Takashi 広島大学, 医歯薬保健学研究科(歯), 教授 (10264053)
• Co-Investigator(Kenkyū-buntansha): 浅野 智志 広島大学, 医歯薬保健学研究科(歯), 助教 (30570535) ; 山脇 洋輔 広島大学, 医歯薬保健学研究科(歯), 助教 (90584061)
• Research Collaborator: Maetani Yuka
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 癌 / 細胞浸潤 / 細胞増殖 / リン脂質代謝 / PRIP / PI3K / PI(3,4,5)P3 / AKT

Outline of Final Research Achievements

The metabolic processes of PI(4,5)P2 into PI(3,4,5)P3 and the subsequent PI(3,4,5)P3-mediated signaling are involved in cell migration and proliferation. Dysfunctions in the control of this pathway can cause human cancer cell migration and metastatic growth. Here we investigated whether phospholipase C-related catalytically inactive protein (PRIP), a PI(4,5)P2-binding protein, regulates cancer cell activity. PRIP expression inhibited cancer cell growth and migration in vitro and metastasis development in vivo. Overexpression of PRIP pleckstrin homology domain, a PI(4,5)P2 binding motif, in cells significantly suppressed cell migration. PI(3,4,5)P3 production was decreased in Prip-overexpressing cells. The association between PI3K and PI(4,5)P2 was significantly inhibited by recombinant PRIP in vitro. Collectively, PRIP regulates the PI(4,5)P2 metabolism, and the suppressor activity of PRIP in PI(4,5)P2 metabolism regulates the tumor growth and migration.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

本研究を通して新たな分子（PRIP）による細胞運動や細胞増殖の制御機構を明らかにすることができた。これにより、PRIPが調節している細胞膜のリン脂質代謝機能の破綻で生じる癌病態の新しい理解に繋がり、新たな創薬標的の提案ができると期待できる。今後は、本研究成果を新しい抗腫瘍薬開発研究に繋げていく。