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两个不同的上皮细胞到介质细胞的过渡程序控制了分离的瘤细胞群体的入侵和炎症
Khalil Kass Youssef1, Nitin Narwade1, Aida Arcas1,2
1Instituto de Neurociencias (CSIC-UMH), Alicante, Spain.
Nature cancer
|October 16, 2024
概括
癌细胞利用不同的上皮转移到介质细胞转移 (EMT) 途径,而不是单一的程序,要么传播或引起炎症. 在这些独特的癌细胞可塑性路径中,SNAIL1和PRRX1是关键因素.
科学领域:
- 细胞生物学 细胞生物学
- 发育生物学是发展生物学.
- 癌症生物学 癌症生物学
背景情况:
- 皮质到介质细胞转换 (EMT) 是胚胎发育,组织修复和癌症进展期间推动细胞可塑性的基本过程.
- 癌症中EMT的特定机制和结果是复杂的,并未完全理解,导致瘤异质.
研究的目的:
- 调查癌症是否存在一个独特的EMT程序.
- 阐明癌症中EMT的细胞轨迹和分子驱动因素.
- 了解不同EMT途径在瘤进展和宿主反应中的功能后果.
主要方法:
- 在癌症细胞系中分析EMT.
- 关于胚胎神经发展的研究.
- 利用纤维化和乳腺癌的小鼠模型.
- 研究了转录因子SNAIL1和PRRX1.1的作用.
主要成果:
- 确定了两个不同的,分离的细胞轨迹,由胚胎类或成年类EMT激活,而不是单一的癌症特异性EMT程序.
- 在这两种轨迹中,SNAIL1 起到先驱作用,而PRRX1 则驱动胚胎类型的侵入性轨迹.
- 证明了轨迹之间的可塑性和相互依赖性;删除Prrx1抑制了转移并增强了抗瘤炎症.
结论:
- 癌症的EMT不是一个单一的程序,而是涉及到分叉轨迹驱动传播或炎症.
- 通过分配功能,EMT在编排瘤内部异质性方面发挥着至关重要的作用.
- 针对特定的EMT轨迹,如PRRX1驱动的侵入性轨迹,可以在预防转移和促进抗瘤免疫力方面提供双重好处.
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