一个Jagged1调节的混合EMT状态识别了胰腺癌干细胞
Linxiang Lan1, Huafu Li2, Shiwei Zhang3
1Research Center, Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China; Digestive Medicine Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China; The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK.
Cell reports
|January 25, 2026
概括
胰腺癌干细胞 (CSCs) 具有杂交的上皮细胞-介质细胞过渡 (EMT) 特性,标记为CD9,驱动瘤生长. Jagged1-Notch信号维持了这种CSC状态,这对于胰腺管腺癌 (PDAC) 异质性和瘤性至关重要.
科学领域:
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
- 细胞异质性 细胞异质性
背景情况:
- 胰腺管腺癌 (PDAC) 呈现出显著的细胞异质性.
- 一个先前识别的PDAC亚群,标记为CD9,启动瘤并促进异质性.
- 瘤发起细胞 (TICs) 对癌症的进展和治疗耐药性至关重要.
研究的目的:
- 为了表征具有混合上皮层-介质细胞过渡 (EMT) 特征的CD9高 (CD9hi) TIC.
- 研究这些混合-EMT CD9hi TICs在PDAC有机体形成和瘤性中的作用.
- 阐明调节这些ICT的信号通路,特别关注Notch信号.
主要方法:
- 具有混合EMT功能的CD9hi TIC的特征.
- 评估有机体形成能力和瘤细胞后代的产生.
- 混合EMT CD9hi细胞的耗尽研究,以评估它们对瘤发生性的必要性.
- 分析Jagged1 (Jag1) 表达及其在TIC自我更新和PDAC细胞分化中的作用.
- 研究Notch通路抑制和Jag1过度表达效应.
主要成果:
- CD9hi TICs表现出混合EMT特征和增强的癌症干细胞特性,包括增加有机体形成和产生各种瘤细胞类型.
- 混合EMT CD9hi细胞的耗尽导致有机体形成的崩和瘤发生能力的丧失.
- 混合-EMT CD9hi 信息和通信技术的升级 Jagged1.
- Jag1 枯竭或 Notch 抑制会影响 TIC 自更新和 PDAC 细胞分化.
- Jag1过度表达增强了TIC自我更新.
结论:
- 具有混合EMT特征的CD9hi TIC对于PDAC中持续的有机体形成和瘤发生性至关重要.
- 在PDAC TIC中,Jagged1介导的Notch信号是PDAC TIC中混合EMT状态的关键调节器.
- 这种信号通路控制TIC自我更新和PDAC细胞分化,有助于瘤异质.
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