Elucidation of molecular mechanisms underlying colorectal tumorigenesis driven by Wnt/c-Myc signaling

2019 Fiscal Year Final Research Report

• Project/Area Number: 16H04692
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor biology
• Research Institution: The University of Tokyo
• Principal Investigator: Kawasaki Yoshihiro 東京大学, 定量生命科学研究所, 客員准教授 (10376642)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: Wnt / c-Myc / lncRNA

Outline of Final Research Achievements

We identified a direct target of c-Myc, termed MYU, and showed that MYU was upregulated in most colon cancers and required for the tumorigenicity of colon cancer cells. Furthermore, we demonstrated that MYU associated with the RNA binding protein hnRNP-K to stabilize CDK6 expression and thereby promoted the G1-S transition of the cell cycle. These results suggest that the MYU/hnRNP-K/CDK6 pathway functions downstream of Wnt/c-Myc signaling and plays a critical role in the proliferation and tumorigenicity of colon cancer cells.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

転写因子であるc-Mycは様々なシグナル経路のハブ因子として機能することが知られています。そのため、c-Mycを直接阻害する薬剤は大きな副作用があると予想されます。したがって、c-Mycが誘発するがんに対してはMYU、hnRNP-K、CDK6による情報伝達の仕組みががんの分子標的薬を創製する上で重要な標的に成り得ると期待できました。