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基质刚度通过CXCR4受体动态调节三阴性乳腺癌信号传递

Kenneth K Y Ho¹, Johanna M Buschhaus^1,2, Anne Zhang¹

¹Center for Molecular Imaging, Department of Radiology, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109, USA.

Scientific reports

|August 12, 2025

概括

刚性细胞外基质 (ECM) 增加癌细胞受体表达和信号,促进三阴性乳腺癌 (TNBC) 细胞迁移. 这突出了ECM机制如何影响癌症进展.

科学领域:

生物物理学的生物物理.
癌症生物学癌症生物学
细胞力学细胞力学

背景情况:

细胞外矩阵 (ECM) 机械刚性影响癌细胞的行为.
癌细胞对ECM硬度和生化信号 (如生长因子) 都有反应.
机械和生化因素对癌细胞功能的综合影响尚不清楚.

研究的目的:

研究ECM硬度如何影响癌细胞表达CXCR4和EGFR.
确定ECM刚度对受体内化和下游信号通路 (Akt,ERK) 的影响.
阐明受体动态在调解ECM硬度对三阴性乳腺癌 (TNBC) 细胞迁移的影响中的作用.

主要方法:

使用了具有定义硬度 (1.5kPa和28kPa) 的弹性支表面 (ESS) 培养盘.
采用单细胞成像技术来分析受体表达和内化.
评估了Akt和ERK信号通路的基底和带刺激激活.

主要成果:

硬基板 (28 kPa) 与软基板 (1.5 kPa) 相比,增加了CXCR4和EGFR表达.
刚性ECM促进了CXCR4更大的依赖连接体的内部化.
增强的ECM刚度增加了基底和体诱导的Akt和ERK激活,并促进了TNBC细胞迁移.

结论:

脑膜硬度显著影响癌细胞受体表达和信号动态.
受体动态,特别是CXCR4,调解了TNBC中刚性ECM的前迁移效应.
这些发现表明,ECM的机械特性是TNBC进展的关键因素.

关键词:

标签: 活动活动活动在CXCR4中,CXCR4是最常见的.埃尔克·埃尔克是什么意思细胞外矩阵是细胞外矩阵.信号传输的动态三阴性乳腺癌是三阴性乳腺癌.

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