一个以YAP为中心的机械传导循环驱动集体乳腺癌细胞入侵
Antoine A Khalil1, Daan Smits2, Peter D Haughton3
1Center for Molecular Medicine (CMM), University Medical Center Utrecht, Utrecht, The Netherlands. a.khalil@umcutrecht.nl.
Nature communications
|June 7, 2024
概括
原I激活了一个涉及Yap蛋白的强度依赖循环,在基底类乳腺癌细胞中. 这个循环通过增强原I对齐和张力来驱动集体癌症的入侵,突出显示了Yap在领导细胞选择中的作用.
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:
- 密集,对齐的原I纤维与领导细胞的集体癌症入侵有关.
- 基底类乳腺癌细胞表达素14 (K14) 并保留上皮特征.
- 领导细胞出现的原I与K14表达之间的相互作用尚未完全理解.
研究的目的:
- 阐明原I影响集体癌症入侵的机制.
- 调查雅普在调解原I驱动癌细胞行为中的作用.
- 要确定K14表达是否对这个过程至关重要.
主要方法:
- 利用乳腺癌类器官在3D原I矩阵中模拟瘤入侵.
- 采用生物化学分析和基因操纵来研究雅普信号通路.
- 在入侵模型和患者衍生样本中评估了Yap和K14的要求.
主要成果:
- 在基底类癌细胞中发现了由原I驱动的依赖力前循环.
- 确定了Yap作为这个循环中的中央机械传感器,独立于K14表达.
- 证明活跃的Yap促进了原I的对齐和张力,进一步激活了Yap.
- 证实了Yap在入侵人类乳腺癌细胞中的存在以及其在体内入侵的必要性.
结论:
- 雅普在集体癌症入侵期间的领导细胞选择中发挥着关键作用.
- 以雅普为中心的,依赖力循环是将瘤微环境与侵入性行为联系起来的关键机制.
- 准Yap可能提供一种治疗策略,以抑制集体癌症入侵.
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