与癌症相关的纤维细胞积极压缩癌细胞并调节机械传导
Jorge Barbazan1,2, Carlos Pérez-González1, Manuel Gómez-González3
1Institut Curie, PSL Research University, CNRS UMR 144, F-75005, Paris, France.
Nature communications
|November 1, 2023
概括
癌症相关纤维细胞 (CAFs) 形成一个囊,通过actomyosin收缩性积极压缩瘤细胞. 这种机械力影响癌细胞YAP局部化和增殖,揭示了瘤进展的新机制.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 生物物理学的生物物理.
背景情况:
- 癌症相关纤维细胞 (CAFs) 是瘤进展的关键参与者.
- CAFs产生过多的细胞外基质 (ECM),在瘤细胞周围形成一个囊.
- 这种囊被认为可以限制瘤生长并增加瘤内压力.
研究的目的:
- 为了研究CAF生产的囊的机械性能.
- 为了确定CAF囊是否能积极压缩癌细胞.
- 为了阐明CAF介导的机械信号传递在瘤中的机制.
主要方法:
- 在体内进行遗传和物理操纵.
- 在体外微型制造和力测量.
- 对CAF力量模式的3D映射.
- 对YAP局部化和癌细胞增殖的分析.
主要成果:
- 在CAF囊积极压缩癌细胞使用actomyosin收缩性,而不是一个被动的障碍.
- 废除CAF收缩性破坏了囊形成和消散压力.
- 压缩CAF是一种内在的特性,独立于癌细胞生长.
- 纤维蛋白线缆协调CAF并传输力.
- 癌细胞感觉到CAF的压缩,改变了YAP的局部化,减少了增殖.
结论:
- CAF囊是一种收缩结构,可以积极压缩癌细胞.
- 这种机械压缩会影响癌细胞的行为和瘤形态.
- 了解CAF收缩性为癌症治疗提供了潜在的治疗点.
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