中心细胞放大促进细胞通过细胞与细胞接触破坏和Rap-1激活促进细胞入侵
Anu Prakash1, Shishir Paunikar1, Mark Webber1
1Lambe Institute for Translational Research, Discipline of Pathology, Centre for Chromosome Biology, University of Galway, Galway H91 V4AY, Ireland.
Journal of cell science
|September 29, 2023
概括
在正常细胞中,单独的中枢细胞放大 (CA) 驱动了早期的瘤样变化. 这一过程破坏了细胞-细胞结合点,并通过Rap-1信号来重塑细胞外基质 (ECM).
科学领域:
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
- 生物化学 生物化学
背景情况:
- 中心细胞放大 (CA) 是人类癌症的标志,有助于瘤发生.
- 单独CA在启动前瘤变化的特定作用需要进一步阐明.
研究的目的:
- 研究单独CA诱导对瘤结构和细胞外矩阵 (ECM) 重塑的机制性贡献.
- 为了确定正常细胞中的CA是否足以诱导早期的前瘤原生表型.
主要方法:
- 在非瘤源的MCF10A乳腺细胞中诱导CA.
- 细胞迁移,入侵和细胞-细胞结合完整性的评估.
- 分析ECM相关蛋白质 (整体蛋白β-3,纤维蛋白-1) 和矩阵金属蛋白酶.
- 使用胚胎异种移植模型进行体内验证.
- 使用GGTI-298进行小GTPase Rap-1信号的药理抑制.
主要成果:
- 在MCF10A细胞中的CA诱导促进了细胞迁移和入侵.
- 观察到上皮细胞-细胞结合的破坏和结合蛋白的改变表达/局部化.
- 集成蛋白β-3,纤维素-1和矩阵金属蛋白酶的高表达促进了细胞-ECM相互作用和ECM降解.
- 在体内,CA诱导的细胞侵入宿主组织,引发炎症反应.
- 抑制Rap-1信号阻断了CA诱导的前瘤原生效应.
结论:
- 单独在正常细胞中诱导CA就足以在几天内产生早期的前瘤变化.
- 通过依赖Rap-1的信号通路,CA促进了入侵和ECM重塑.
- 这些发现突出了CA作为癌症发展的早期驱动因素,影响细胞-细胞粘附和瘤微环境.
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