Diversity of the canonical WNT signaling pathway in gastrointestinal epithelial stem cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07972
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: Doi Tomomitsu 産業医科大学, 医学部, 講師 (70437218)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 幹細胞 / βカテニン / p300 / CBP / タンパク質間相互作用

Outline of Final Research Achievements

Stem cells are important for the renewal of the digestive tract epithelium, and WNT/β-catenin signaling plays a central role in controlling stem cell self-renewal and differentiation. Abnormalities in this signaling lead to carcinogenesis. β-catenin binds to TCF and controls transcription, but binding to CBP or p300 is the branching point of the signal, and c-JUN controls the binding of the p300/β-catenin complex to the genome. In this study, we discovered that β-catenin/c-JUN binding is specifically found at the base of the crypts of the small intestine. We also screened several compounds that induce differentiation in cancer cells.

Free Research Field

腫瘍

Academic Significance and Societal Importance of the Research Achievements

WNT/β-cateninシグナルは多くの癌で活性化されており、その制御は癌治療の鍵となる。本研究では、CBPとp300という二つのコアクチベーターが、幹細胞の自己複製と分化の制御において異なる役割を果たしていることを示した。これにより、より効果的で副作用の少ない癌治療薬の開発が期待される。