Integrated understanding of intercellular communication and contraction forces

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K21411
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 44:Biology at cellular to organismal levels, and related fields
• Research Institution: Kyoto University
• Principal Investigator: Fujita Yasuyuki 京都大学, 医学研究科, 教授 (50580974)
• Project Period (FY): 2020-07-30 – 2022-03-31
• Keywords: 細胞競合 / 収縮力 / 牽引力顕微鏡 / カルシウムスパーク

Outline of Final Research Achievements

When an oncogenic mutation occurs within a monolayer of epithelial cells, cell competition occurs between normal and the newly emerging transformed cells. However, the molecular mechanisms of cell competition still remain largely unknown.
In this study, we have demonstrated that a transient upsurge of intracellular calcium occurs in normal cells neighboring transformed cells, which is termed ‘calcium spark’. In addition, by analyzing various physical parameters, we have found that compressive forces are imposed onto normal cells neighboring transformed cells, which induces the increased membrane tension. The increased membrane tension then leads to the occurrence of calcium sparks mediated by mechano-sensitive calcium channel.

Free Research Field

分子腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究によって、変異細胞に隣接した正常細胞では、様々な物理的、化学的な変化が生じ、その結果、変異細胞の上皮細胞層からの排除を促進していることが明らかになった。これまで、細胞競合における細胞の物理的な変化については、ほとんど報告がなく、細胞競合研究分野に新たな見地を与える研究成果であると高く評価できる。また、これらのデータは、これまでブラックボックスであったがんの超初期段階で起こるプロセスの一端を明らかにするものであり、今後のがんの予防的治療薬の開発にもつながり得る研究成果であると言えよう。