Defective syste-level regulation of Aurora B underlies chromosomal instability

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K16727
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: JO Minji 公益財団法人がん研究会, がん研究所 実験病理部, 研究員 (80808866)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 染色体異数体化 / 染色体不安定性 / Aurora Bキナーゼ / non-coding RNA / HP1

Outline of Final Research Achievements

Chromosomal passenger complex (CPC) ensures accurate chromosomal segregations during mitosis through releasing incorrect attachments of kinetochores and centromeres. We previously reported that the function of CPC is allosterically increased by interaction with heterochromatin protein 1 (HP1) and the amount of HP1-bound CPC is decreased in a wide of cancer cells. Here, we aimed to understand the reduction of HP1-involvement in cancer cells and found that the extent of HP1 assembly at centromeres is closely related to ploidy alteration and transcriptional regulation, affecting chromosomal instability in cancer cells.

Free Research Field

細胞生物学、腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

細胞分裂期における頻繁な染色体分配の失敗は染色体不安定性と呼ばれ、がんの治療抵抗性や予後と相関する。また、がんの進展とともに多く見られる特徴であることから、このがんの性質に着目した研究成果は、進行がんの診断・治療への応用が強く期待される。本研究によって、正確な染色体分配を維持する染色体パセンジャー複合体(CPC)の機能制御において、染色体異数体化と転写の関連性が見出され、がん細胞の染色体不安定性を引き起こす機構を理解する手がかりとなる知見を得た。