NOX1和NPY1R标记了在体内作为癌症起源的区域结肠干细胞群，这一成果由新加坡A*STAR分子与细胞生物学研究所Nick Barker研究组经过不懈努力而取得。相关论文于2025年9月2日发表在《自然—细胞生物学》杂志上。

在这里，研究组报告了NOX1和NPY1R作为细胞表面标记物在LGR5⁺干细胞中富集，分别主要存在于盲肠和只存在于结肠中部和远端。在NOX1⁺或NPY1R⁺干细胞主题为CreERT2的小鼠系中，Wnt信号的选择性失调驱动结肠癌的发生，主要分别在盲肠和直肠内，使这些干细胞群成为结肠癌的重要来源。Wnt信号和致癌Kras的选择性条件激活以及这些干细胞区室中TRP53的缺失导致晚期侵袭性癌症的发展。这项研究确立了CreERT2驱动因子作为研究干细胞对结肠癌的贡献的有价值的工具。

据介绍，目前的结直肠癌小鼠模型要么缺乏结肠特异性，限制了向更晚期疾病的进展，要么排除了对驻留干细胞作为癌症起源的评估。

附：英文原文

Title: NOX1 and NPY1R mark regional colon stem cell populations that serve as cancer origins in vivo

Author: Gasnier, Maxime, Chen, Tanysha Chi-Ying, Yada, Swathi, Sagiraju, Sowmya, Yoshikawa, Yusuke, Perna, Stefano, Lim, Hui Yi Grace, Lee, Bernett, Barker, Nick

Issue&Volume: 2025-09-02

Abstract: Current colorectal cancer mouse models either lack colon specificity, limiting progression towards more advanced disease, or preclude evaluation of resident stem cells as cancer origins. Here we report the identification of NOX1 and NPY1R as cell-surface markers enriched in LGR5+ stem cells predominantly within the caecum and exclusively within the middle and distal colorectum, respectively. Selective dysregulation of Wnt signalling in NOX1+ or NPY1R+ stem cells using CreERT2 mouse lines drives colon cancer initiation, predominantly within the caecum and rectum respectively, establishing these stem cell populations as important sources of colon cancer. Selective conditional activation of Wnt signalling and oncogenic Kras in combination with loss of TRP53 in these stem cell compartments resulted in the development of advanced, invasive cancers. This study establishes CreERT2 drivers as valuable tools for studying stem cell contributions to colon cancer.

DOI: 10.1038/s41556-025-01763-1

Source: https://www.nature.com/articles/s41556-025-01763-1