Study on the remodeling of energy metabolism of cancer cells with a novel technology of isolating cells based on ATP concentrations

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K22386
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
• Research Institution: Kyoto University
• Principal Investigator: Imamura Hiromi 京都大学, 生命科学研究科, 准教授 (20422545)
• Project Period (FY): 2019-06-28 – 2022-03-31
• Keywords: 解糖系 / 酸化的リン酸化 / ATP / ワールブルグ効果 / CRISPR / FRET / 蛍光バイオセンサー / フローサイトメトリー

Outline of Final Research Achievements

We searched for genes involved in the highly glycolysis-dependent synthesis of ATP in cancer cells. First, we developed an improved fluorescent ATP biosensor with high performance at room temperature (25°C) to measure intracellular ATP concentration using a flow cytometer. Next, we performed genome-wide gene disruption of cancer cells. After glycolysis was inhibited, cells with decreased ATP concentration were isolated using a flow cytometer. By repeating the process of isolating cells by flow cytometry, we succeeded in obtaining a cell population with low dependence of ATP synthesis on the glycolytic pathway.

Free Research Field

生物物理学、細胞生物学

Academic Significance and Societal Importance of the Research Achievements

がんは日本国民の死亡原因の第１位であり、２人に1人が生涯のうちに罹患する。一方、がんの治療法は未だ十分とは言い難い。がん細胞は正常細胞とは異なり、解糖系に極めて強く依存したATP合成をおこなっていることが知られているが、その詳しい仕組みはまだ解明されていない。今回の研究成果は、がん細胞の特異なエネルギー代謝の仕組みを明らかにするための足がかりになるものである。