Research on pH-dependent cell death program that occurs in the mitotic phase of cancer cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K19406
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 50:Oncology and related fields
• Research Institution: Kyoto University (2022-2023); Osaka University (2021)
• Principal Investigator: Miki Hiroaki 京都大学, 工学研究科, 教授 (80302602)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: 細胞死

Outline of Final Research Achievements

In this study, we analyzed the unique pH-dependent cell death that occurs in cells that highly express the oncogenic protein PRL. When cells overexpressing PRL were cultured under weakly alkaline conditions, cell death accompanied by abnormal chromosome segregation occurred during the M phase of the cell cycle. Although cell death was not noticeable in a physiological pH environment, some abnormality was observed in chromosome alignment during the division phase, and further abnormalities in the number of chromosomes occurred with continued culture. Abnormalities in the number of chromosomes are also a characteristic of malignant cancer cells, and can be considered as the basic molecular mechanism for the progression of cancer malignancy due to PRL overexpression.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

がん悪性化にはたらくPRLの分子機能解析から見つけたユニークな細胞死に着目した解析を進めることで、細胞分裂期の染色体アラインメントにおける異常を新たに見つけることができた。実際にPRL高発現細胞を培養し続けることで染色体数の異常が生じることも示され、新たながん悪性化進展機構の解明にもつながる重要な研究成果と考えられる。また、細胞のエネルギー状態に応じて活性化されるAMPキナーゼのキネトコア特異的な活性化異常を見出しており、このキナーゼの活性調節における興味深い一面を明らかにできた点でも重要な意義がある。