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恢复机械表型可以逆转ECM丰富的声癌的恶性特性
Jasmin Kaivola1, Karolina Punovuori2, Megan R Chastney1
1Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
bioRxiv : the preprint server for biology
|October 7, 2024
概括
声癌 (VFC) 会使组织变硬并改变细胞的行为. 机械力量可以减少癌症的生长,这表明YAP/TAZ向是这种机械敏感恶性瘤的潜在治疗方法.
科学领域:
- 在瘤学瘤学.
- 生物物理学的生物物理.
- 机械生物学 机械生物学
背景情况:
- 细胞外基质 (ECM) 和基质刚度的增加是已知的固体瘤进展的驱动因素.
- 在癌症中,机械活跃组织 (如声) 中的机械传导是鲜为人知的.
研究的目的:
- 调查机械传导和ECM变化在声癌 (VFC) 进展中的作用.
- 探索生理机械力量对VFC细胞的影响,并确定潜在的治疗点.
主要方法:
- 在不同阶段 (T1-T3) 进行非癌性 (NC) 和患者衍生的VFC细胞的比较.
- 分析ECM组件,细胞表面受体和细胞运动模式.
- 在体外实验中模仿声组织运动 (伸展/振动) 的实验,以及对YAP/TAZ信号的评估.
- 在VFC瘤上进行多重复合免疫组织化学,以关联ECM,YAP水平和患者存活率.
- 在体外测试YAP-TEAD抑制剂.
主要成果:
- VFC表现出ECM组件的升高调节和组织度的增加.
- VFC的进展与细胞表面受体异质性,改变的整蛋白局部化和集群集体细胞运动性有关.
- 模仿生理运动降低了VFC细胞中的致癌核β-catenin和YAP水平.
- 瘤ECM含量和核YAP水平与患者存活率相关.
- 在实验室中,VFC细胞对YAP-TEAD抑制剂表现出敏感性.
结论:
- 声癌是一种机械敏感的恶性瘤.
- 恢复瘤机械表型或准YAP/TAZ信号,为VFC提供了可行的治疗策略.
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