Extracellular diacyl phospholipids

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K22508
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 48:Biomedical structure and function and related fields
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Sasaki Takehiko 東京医科歯科大学, 難治疾患研究所, 教授 (50333365)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Keywords: リン脂質

Outline of Final Research Achievements

Structure-activity relationship of macrophage activation by extracellular PIP3 was clarified using cytokine production as an indicator. The findings suggested the existence of specific receptors.
We found that extracellular PIP3 induced cytoskeletal reorganization in various cancer cell lines. About 50 cultured cell lines were examined, but only some of them were sensitive. Gene expression in 30 breast cancer cell lines was analyzed by RNA seq, and membrane proteins that correlated with PIP3 sensitivity were narrowed down to candidate receptor proteins.
We conducted receptor screening based on the working hypothesis that the PIP3 receptor belongs to the GTP-binding protein-coupled receptor family.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

PIP3が新しいホルモン/オータコイドであれば、現在の膜構成因子としてのドグマでは目が向けられていない、PIP3の新規の生理活性とその発現機構が明らかになるなど、これまで見逃されていた生体調節機構の発見につながる可能性があることから、本研究は細胞膜脂質研究をはじめ生命科学の様々な研究分野の体系や考え方の方向を大きく転換する潜在性を有すると考えている。