Molecular mechanisms of cytokinesis completion and cell fate decision after cytokinesis failure
| Project/Area Number |
17K07172
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | Kyushu University |
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Principal Investigator |
Iimori Makoto 九州大学, 薬学研究院, 准教授 (20546460)
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| Co-Investigator(Kenkyū-buntansha) |
北尾 洋之 九州大学, 薬学研究院, 教授 (30368617)
沖 英次 九州大学, 大学病院, 講師 (70380392)
佐伯 浩司 群馬大学, 医学系研究科, 教授 (80325448)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 染色体不安定性 / 四倍体細胞 / heterogeneity / 細胞質分裂 / OGG1 / 酸化ストレス / ミッドボディ / 細胞・組織 |
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| Outline of Final Research Achievements |
Chromosomal instability, one of the most prominent features of tumour cells, causes aneuploidy. Cytokinesis failure leads to production of tetraploid cells, which is thought to be an intermediate on the path to aneuploidy.
In this study, we found that knockdown of OGG1 induced a delay in abscission during cytokinesis. Next, we showed that the mitotic kinesin Eg5 plays an important role in determining spindle polarity (e.g., multipolarity vs. bipolarity) in tetraploid cells and demonstrated that spindle multipolarity and subsequent cell behaviour decisions are determined by the balance between forces generated by mitotic kinesins, including Eg5, Kif15 and HSET. Our data provide a novel possible explanation for the mechanistic relationship between Tetraploidisation and chromosomal instability; a high level of Eg5 can accelerate the acquisition of aneuploidy and chromosomal heterogeneity in tetraploid parental cells, contributing to tumour progression and resistance to anti-tumour drugs.
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| Academic Significance and Societal Importance of the Research Achievements |
がんおける最も顕著な特徴のひとつである染色体不安定性はがん化の過程における悪性形質の獲得や抗がん剤耐性の獲得の要因であると考えられている。しかし四倍体細胞を中間体とした異数性形成メカニズムは十分に理解されていない。
本研究成果として，まず細胞質分裂に関与する新規因子として同定したOGG1の関与する生物学的意義と分子機構のさらなる解析は，細胞質分裂の研究分野における学術的基盤の確立に役立つことが期待される。さらに四倍体細胞を中間体とした異数性形成分子モデルは，がんの不均一性およびそれにともなうがん悪性化や抗がん剤耐性獲得などがん病態を根幹的に理解することにつながると考えられる。
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Report
(4 results)
Research Products
(4 results)
