A new mitotic surveillance mechanism in nucleolus and its application to cancer therapy

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K07221
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Kagoshima University
• Principal Investigator: Kawahara Kohichi 鹿児島大学, 医歯学域医学系, 准教授 (00400482)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 核小体ストレス応答 / 細胞分裂 / TP53 / がん分子標的治療薬 / がん治療感受性マーカー

Outline of Final Research Achievements

A nucleolar stress response mechanism in which abnormal nucleolar function increases the tumor suppressor p53 and suppresses cell proliferation has been identified. In present study, we found that 1) the nucleolar stress response may be a novel mitotic surveillance mechanism that suppresses cell proliferation by mitotic abnormalities, 2) we identified novel compounds that induce the nucleolar stress response and kill tumor cells by increasing P53, and 3) regulators of the nucleolar stress response are involved in the sensitivity of gastric cancer to 5FU treatment.

Free Research Field

分子腫瘍学

Academic Significance and Societal Importance of the Research Achievements

分裂期における核小体ストレス応答の役割が明らかになり、これまで不明であった、分裂期の核小体のダイナミックな再編成の意義の解明につながる。また、新規作用機序をもつP53経路を活性化させるがん分子標的治療薬や、核小体ストレス応答の分子の発現で再発や予後を予測できる診断薬の開発も見込まれ、個別化医療を指向した新たながん治療戦略の開拓が期待される。