2022 Fiscal Year Final Research Report
Phosphoinositides' diversity and function
Project/Area Number |
20H03433
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 48040:Medical biochemistry-related
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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)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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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.
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Free Research Field |
細胞生物学
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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。
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