Elucidation of the mechanism for determining the winner of cell competition among cancer cells with genetic diversity

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23929
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: National Cancer Center Japan
• Principal Investigator: Yamamori Morita Tomoko (森田智子) 国立研究開発法人国立がん研究センター, 先端医療開発センター, 特任研究員 (10767750)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: がん / 染色体不安定性 / 細胞競合

Outline of Final Research Achievements

As a model of chromosomal instability adaptability, we established a cell line that is stably aneuploid. During the establishment of the cell line, about 90% of cells died, indicating that being aneuploid is highly stressful to the cells. Approximately 10% of surviving cells are mainly tetraploid and have the same proliferative capacity as the parent cells. As compared to the parent cells, the aneuploid cells showed a characteristic morphology similar to senescent cells and high positive rate of SA-b-galactosidase. In addition, under certain conditions, aneuploid cells showed a marked decrease in ATP levels. From the results of various omics analysis, it is considered that aneuploid cells adapt to the environment by changing amino acid / lipid metabolism pathways without causing gene mutations or structural changes in transcriptional activation regions.

Free Research Field

染色体不安定性

Academic Significance and Societal Importance of the Research Achievements

研究対象はがん細胞が持つ特徴の一つ、染色体不安定性です。
染色体不安定性は細胞にとってストレスが大きい現象で、約9割の細胞が死んでしまう事を明らかにしました。一方、約10%の細胞はストレスを克服して生き残り、増殖します。生き残った細胞が持つ特徴や個性を特定し、がん治療の標的にすることを目的としています。
今回の研究成果は染色体不安定性を持つ異数体化細胞が、親細胞と同じように増殖する一方、細胞老化の特徴を併せ持つことを明らかにしました。また、特定の条件下では細胞が脆弱性を示すことが分かりました。各解析結果を統合すると、異数体化細胞は代謝経路を変化させることで周囲の環境に適応していると推測できます。