Understanding of Wnt-addicted cancer cells using comprehensives transcriptome data

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07563
• 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: The University of Tokyo
• Principal Investigator: Yamaguchi Kiyoshi 東京大学, 医科学研究所, 講師 (50466843)
• Co-Investigator(Kenkyū-buntansha): 古川 洋一 東京大学, 医科学研究所, 教授 (20272560)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 大腸がん / 肝がん / Wnt/β-cateninシグナル / 転写調節機構 / 遺伝子発現

Outline of Final Research Achievements

The Wnt/β-catenin signaling pathway has been shown to be activated in various types of cancer including colon and liver cancer. In this study, we identified two novel target genes of this pathway, MOSPD1 (motile sperm domain containing 1) and ODAM (odontogenic, ameloblast associated), in colorectal and liver cancer, respectively. In addition, we found their Wnt-dependent enhancers in the 3’-flanking region and 15 kb-upstream region of MOSPD1 and ODAM, respectively. This study also disclosed that ODAM regulates cell cycle progression and proliferation of hepatoma cells. Besides, we identified another target gene, VSNL1 (visinin-like 1) using the near-haploid human cell line HAP1, and showed that VSNL1 plays a crucial role in the anti-apoptotic property of colorectal cancer cells. Further investigation of the biological role of these molecules will contribute to the profound understanding of physiological and pathological processes played by the Wnt signaling pathway.

Free Research Field

分子腫瘍学

Academic Significance and Societal Importance of the Research Achievements

Wnt/β-cateninシグナル伝達経路の異常な活性化は、様々ながん種の発がんや細胞の生存、幹細胞の増殖と分化の調節、最近ではがん免疫回避機構に関与することが報告されている。そのため同経路は、がんの再発や薬剤耐性化の解決に繋がる有望な標的として治療薬開発が行われてきた。しかしながら、実際の臨床で投与可能な治療薬の開発には至っていないのが現状である。我々の研究成果は、Wntシグナルの多種多様な生物学的プロセスの理解に役立つだけでなく、これら下流分子を標的とする新しい抗がん剤開発への展開が期待される。