Elucidation of the mechanical regulation of YAP activation during maintaining organ homeostasis and regeneration

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K22657
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0702:Biology at cellular to organismal levels, and related fields
• Research Institution: Yamaguchi University
• Principal Investigator: Tao Hirotaka 山口大学, 大学院医学系研究科, 助教 (30425417)
• Project Period (FY): 2020-09-11 – 2023-03-31
• Keywords: YAP

Outline of Final Research Achievements

We aimed to understand the molecular mechanism of cancer progression as a disruption of YAP mechanical homeostasis at the single-cell level. We proceeded with the analysis of the following three projects: 1) spatio-temporal protein analysis of YAP activation, 2) quantitative analysis of the relationship between the mechanical properties of living organisms, mechanical responses, and YAP activation, and 3) analysis of the types and functions of YAP-activated cells. As for human specimen collection for this analysis, 30 colorectal cancer specimens have already been obtained to date. The CODEX equipment and reagents have already been delivered to the University and analysis has begun. In addition, the equipment for 2) and 3) and the creation of YAP reporter mice are in progress.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

本研究でのヒトおよびマウスのがん組織を用いたCODEX法による位置情報を保持した状況で多次元プロテオミクスデータ解析により、公開されている蓄積されたビックデータと比較し、網羅的に解析することで、がん発症、進展過程における微小環境下で一見無秩序に混在するがん細胞群と自己免疫細胞群との空間的分布を数細胞レベルでのYAP活性細胞と隣接相関関係に法則性を見出す。加えて、力学的特性を合わせて解析することで、がん化しやすい微小環境の同定を行う。本研究は、将来的にはそのがん微小環境領域を作り出さない薬剤投与の検討を行う基盤となる研究ある。