Principle of chronic centrosome aberrations in whole-genome duplicated cells and its contribution to cellular heterogeneity

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03219
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 44010:Cell biology-related
• Research Institution: Hokkaido University
• Principal Investigator: Uehara Ryota 北海道大学, 先端生命科学研究院, 准教授 (20580020)
• Co-Investigator(Kenkyū-buntansha): 塚田 祐基 名古屋大学, 理学研究科, 助教 (80580000)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 染色体倍加 / 中心体 / 倍数性

Outline of Final Research Achievements

In this study, we aimed to elucidate the principle and significance of centrosome hyperactivation associated with whole-genome duplication (WGD), a cellular abnormality common in 30% of cancers. We found that this phenomenon is caused by an increase in the accumulation of centrosomal proteins resulting from the doubling of the gene dosage of a centrosome scaffolding gene upon WGD. By developing a method to cancel this centrosome hyperactivation artificially, we found that this phenomenon does not play an adaptive role in the proliferation control of WGD cells. However, contrary to our initial expectation, we found that the centrosome hyperactivation made WGD cells more fragile in centrosomal structural homeostatic regulation, suggesting the feasibility of WGD cell-selective suppression through targeting their fragility.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

染色体倍加は個体発生、疾病、進化など多様なプロセスを駆動する細胞現象であり、染色体倍加が細胞機能を変化させる過程とその原理の解明は、これら広範な生命プロセスを理解し制御するために欠かすことができない。本研究は、染色体倍加細胞が引き起こす具体的細胞制御変化として中心体構造制御の脆弱化を突き止め、その分子基盤を明らかにした点に学術的意義がある。さらに、この脆弱性を標的とすることで、疾病の要因となりうる染色体倍加細胞の選択的な細胞分裂阻害が可能であることを示した点に医学面での社会的意義がある。