核变形调节了与癌症相关的纤维细胞中的YAP动态
Bashar Emon1, M Saddam H Joy1, Luke Lalonde1
1Mechanical Science & Engineering.
Acta biomaterialia
|November 17, 2023
概括
核变形,而不是基质刚性,驱动癌细胞中YAP的核运输. 这一发现在2D和3D环境中观察到,表明核变形作为瘤中YAP激活的潜在生物标志物.
科学领域:
- 细胞生物学 细胞生物学
- 生物物理学的生物物理.
- 癌症研究 癌症研究
背景情况:
- 是的相关蛋白 (YAP) 是癌症进展的关键驱动因素,通常由硬的瘤环境激活.
- 细胞内力量和核变形 (ND) 与YAP定位有关,但它们在3D环境中的作用尚不清楚.
研究的目的:
- 调查核变形在YAP局部化中的作用,跨不同基板尺寸和硬度.
- 确定周核力和核膜曲率是否是YAP激活的关键调节者.
- 开发YAP转位的动力模型.
主要方法:
- 在2D,2.5D和3D基板上培养人类结肠癌相关纤维细胞 (CAFs).
- 量化细胞内力量和核变形.
- 分析YAP局部化和核膜曲率.
- 开发YAP动力学的随机模型.
主要成果:
- YAP核转位取决于核变形的程度,独立于基板的维度和刚度.
- 周核力和核膜曲率与YAP激活有很强的相关性.
- 瘤样本显示了ND和YAP核定位之间的关联.
- 一个随机模型揭示了YAP核转位概率和居住时间的权力定律关系.
结论:
- 核变形,而不是整体刚性或总力,是YAP核转移的关键因素.
- 核变形和相关的膜曲率是癌症中YAP激活的潜在生物标志物.
- 一个新的动力模型提供了对YAP动态和值激活的洞察.
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