Phosphoinositides' diversity and function

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03433
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 48040:Medical biochemistry-related
• 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): 2020-04-01 – 2023-03-31
• Keywords: リン脂質 / 疾患モデル

Outline of Final Research Achievements

Phosphoinositides of cell membranes have diverse physiological functions depending on the phosphorylation state of the head group, and their metabolic aberrations are implicated in various diseases. We have recently developed a comprehensive phosphoinositide measurement method to elucidate the biological significance of their acyl group diversity, which remains largely unknown. In this study, we identified MTMR3, a phosphatase that regulates PI(3)P levels in pancreatic cancer, and found that the PI(3)P molecular species regulated by MTMR3 promotes pancreatic cancer cell growth.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

新たに膵臓がん細胞で増加したPI(3)Pの下流分子の探索を行い、PI(3)P結合ドメインを持つWDFY1が膵臓がん細胞の増殖に関わることを明らかにした。MTMR3／PI(3)P／WDFY1という新規シグナル経路が、膵臓がん細胞の増殖・悪性化に寄与することを見出した。さらに、MTMR3ノックアウトマウスががんを好発することを初めて見出した。今後、PI(3)P分子種レベルの計測および発がん表現型の解析を進め、難治性がんの代表である膵臓がんの発症メカニズム解明と、新規治療標的を提示できる。