Possible role of AKT in chromosome seggregation, instability and aneuploidy

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06632
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Tokyo University of Science (2020); Yokohama College of Pharmacy (2019); Keio University (2018)
• Principal Investigator: Noguchi Kohji 東京理科大学, 薬学部薬学科, 教授 (80291136)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: AKT / 細胞分裂 / キナーゼ

Outline of Final Research Achievements

The purpose of this study was to clarify the role of cancer-related kinase AKT in chromosome instability and its regulatory mechanism. We found that in metaphase, AKT1 and AKT3 were localized to partially overlap Aurora kinase in the central spindle, and that treatment with AKT inhibitors multipolarized the tubulin spindle that acts on chromosome division. Furthermore, we found KIF23 as a new target molecule candidate for AKT. Phosphorylation of KIF23 by AKT was found to be involved in the localization of KIF23 to the midbody during cell division, demonstrating that AKT3 functions in the cell division mechanism.

Free Research Field

生物系薬学

Academic Significance and Societal Importance of the Research Achievements

細胞分裂不全などで生じた核の多倍数化細胞や異数体性の細胞は最終的に細胞死を起こすが、なぜ異数体性がん細胞が無限増殖できるのかという点については未解明である。本研究で、異数体性がん細胞における染色体不安定性の動的制御機構においてがん関連キナーゼのAKTが関与するメカニズムが解明できれば、新しいがん治療戦略の開発にも貢献できると期待される。