Mechanism of collective invasion of cancer cells based on the regulation of Golgi-derived microtubules

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K07575
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Fukushima Medical University
• Principal Investigator: Nishita Michiru 福島県立医科大学, 医学部, 教授 (30379359)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 微小管 / 癌浸潤 / ゴルジ体 / 細胞極性

Outline of Final Research Achievements

Leader cells within a cancer cell cluster exhibit high motility and polarity, driving collective invasion. However, the mechanisms behind leader-cell fate determination and the expression of their characteristics remain unclear. In this study, we focused on Golgi-derived microtubules, which regulate cell polarity, aiming to elucidate their organizational mechanisms in leader cells and their roles in invasion characteristics. We evaluated the collective invasive ability of human colon cancer cells in Matrigel and found that the IFT20 protein, which is involved in the formation of primary cilia, promotes collective invasion. Additionally, we discovered that IFT20 plays a role in forming polarized and stabilized Golgi-derived microtubules characteristic of leader cells and is involved in the activation of c-Src in the Golgi apparatus.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究の学術的意義は、リーダー細胞のゴルジ体微小管の構築が癌細胞の集団浸潤に重要な役割を持つことを見出した点にある。特に、IFT20がリーダー細胞の極性化および安定化したゴルジ体微小管の形成に関与することを示したことで、癌細胞の集団浸潤のメカニズムに新たな知見を提供した。社会的意義としては、リーダー細胞の特性とその制御機構の一部を明らかにしたことで、癌の新たな治療法開発に繋がる可能性を示した点にある。ゴルジ体微小管を標的とした治療法が転移性癌の抑制に有効であることが期待される。