Posttranscriptional mechanism of Hippo pathway regulation

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07590
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Kobe University
• Principal Investigator: Otani Junji 神戸大学, 医学研究科, 助教 (10770878)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: Hippo経路

Outline of Final Research Achievements

This study aims to identify novel drug targets to inhibit the activation of the transcription coactivators YAP and transcription factor TEAD, which promote cancer cell growth. Whole genome siRNA library screening was performed using cell lines with high sensitivity for the activity of oncogenic gene transcription by YAP-TEAD. The results revealed that RNABP, a post-transcriptional regulator of mRNA, potently activates the transcriptional activity of YAP-TEAD and contributes to cancer cell proliferation, invasion, and migration. RNABP activates YAP-TEAD by suppressing the expression of VGLL4, a YAP inhibitor.

Free Research Field

生物学

Academic Significance and Societal Importance of the Research Achievements

Hippo-YAP経路は、がんの重要なドライバー経路であることが明らかになりつつある。本研究では1分子の発現抑制により最も強くYAP-TEADによる転写活性を阻害する遺伝子を同定し、そのYAP-TEADへの作用機序の解明、阻害剤開発によって癌撲滅に貢献することを目指したものである。本研究から、mRNAの転写後調節機構が細胞の運命決定に重要な役割を持っていることが明らかになった。