癌细胞感知到固体压力,通过CKAP4相位分离介导的微管子分支来增强转移
Xing Sun1,2, Yangyang Zhou2, Shengjie Sun1
1Department of Hematology, the Second Xiangya Hospital, Molecular Biology Research Center, Center for Medical Genetics, School of Life Sciences, Hunan Province Key Laboratory of Basic and Applied Hematology, Central South University, Changsha, Hunan, China.
Cell discovery
|November 11, 2024
概括
癌细胞通过细胞骨相关蛋白4 (CKAP4) 感知固体压力,从而触发液体-液体相分离. 这一过程重塑了微管,增强了细胞运动性,促进了转移.
科学领域:
- 在瘤学瘤学.
- 生物物理学的生物物理.
- 细胞生物学 细胞生物学
背景情况:
- 固体压力是瘤的一个关键特征,与转移和不良预后有关.
- 癌细胞检测和响应固体压力的分子机制尚未完全理解.
研究的目的:
- 研究细胞骨相关蛋白4 (CKAP4) 在癌症中感知固体应激中的作用.
- 阐明CKAP4对癌细胞运动和转移有所贡献的分子机制.
主要方法:
- 临床数据分析将瘤应激与CKAP4表达相关联.
- 在体外研究检查CKAP4对固体应激的反应,使用液-液相分离.
- 显微镜和生化分析分析CKAP4-微管相互作用和信号传递.
主要成果:
- 在转移性瘤中,固体应激的增加与CKAP4表达的增加有关.
- CKAP4充当细胞内机械传感器,在应对固体应力时经历液态-液态相分离.
- CKAP4 puncta与微管结合,改变其结构并增强癌细胞的扩散和运动性.
- CKAP4的内在无序区域 (IDR1和IDR2) 分别介导微管结合和相分离,受Cav1.2通道的影响.
结论:
- 在癌细胞中,CKAP4是固体应激感应的新型媒介.
- 由CKAP4驱动的微管体重塑增强了癌细胞的运动性,并促进了转移.
- 这项研究揭示了一个新的机制,将瘤的物理特性与癌细胞生物学和恶性病变联系起来.
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