Understanding cancer stem cells and targeting colorectal cancer stem cells for therapy via isolation using cellular characteristics

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09056
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Osaka University
• Principal Investigator: Uemura Mamoru 大阪大学, 大学院医学系研究科, 講師 (10528483)
• Co-Investigator(Kenkyū-buntansha): 高橋 秀和 大阪大学, 大学院医学系研究科, 特任講師(常勤) (10528508)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 大腸癌 / 癌幹細胞 / 低プロテアソーム活性 / 低酸素

Outline of Final Research Achievements

Our research targeted the low proteasome activity (LPA), a characteristic of colorectal cancer stem cells (CSCs). We isolated LPA-expressing cells using an imaging vector, confirming their tumorigenicity. We investigated the LPA-tumorigenicity link and changes in gene expression under LPA.
A gene in the Wnt pathway was suppressed in colorectal cancer. Its forced expression reduced cell proliferation, showing its tumor-suppressive role. The gene's knockout didn't lead to spontaneous carcinogenesis in mice. We're now working on a carcinogenesis model.
We focused on long-term hypoxia-induced genes, critical for malignancy and treatment resistance. Unlike short-term hypoxia-responsive genes, the long-term ones solidified changes in proliferation and CSC traits, irreversibly. We're studying if these changes are epigenetically regulated.

Free Research Field

大腸癌

Academic Significance and Societal Importance of the Research Achievements

本研究では、大腸癌幹細胞(CSC)の低プロテアソーム活性(LPA)に注目し、新たながん治療戦略の可能性を探求しました。Wnt経路の上流遺伝子の発現抑制による癌細胞の増殖能低下は、新治療戦略への可能性を含むものと思います。また、長期低酸素環境下での遺伝子発現変化を分析し、悪性度や治療抵抗性に関与する遺伝子群を特定し、これらがエピジェネティックに制御される可能性は、新たな視点を提供するものと思われます。
これらの成果は、がん研究の新領域を開き、治療法開発への道筋を示し、学術的・社会的意義を有すると思われます。