集成蛋白-Piezo1轴驱动ECM重塑和入侵3D乳腺上皮质
Kabilan Sakthivel1,2, Anna Kotowska3, Zhimeng Fan1,2
1Division of Oncology, Department of Clinical Sciences, Lund University, Lund, 22100, Sweden.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|October 13, 2025
概括
组织硬化通过改变细胞矩阵相互作用驱动癌症的入侵. 成熟的上皮结构通过整合蛋白-FAK-Piezo1信号来重塑其细胞外基质 (ECM),在癌症进展过程中创建侵入性利基.
科学领域:
- 生物医学工程 生物医学工程
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
背景情况:
- 组织硬化是癌症进展的关键因素,影响细胞行为和入侵.
- 成熟的上皮结构对其本源细胞外基质 (ECM) 中的机械线索的反应尚未完全理解.
研究的目的:
- 调查成熟的上皮结构如何响应其本土ECM内的机械硬化.
- 揭示驱动ECM重塑和侵袭的分子机制,以应对组织硬.
主要方法:
- 使用3D现场硬化水凝系统来调节成熟正常乳腺周围的硬度.
- 分析了ECM重塑,上皮细胞行为和分子信号通路.
主要成果:
- 组织硬化诱导了表皮重塑的两个不同的阶段:快速的ECM破坏/分泌和延迟的入侵.
- 在入侵阶段观察到纤维内素的重塑和拉米林的重新沉积,这与阿西纳的增殖相吻合.
- 确定了α3β1-和α5β1-整合素-焦点粘附激酶 (FAK) 信号,激活Piezo1,作为关键介质.
结论:
- 成熟的上皮结构动态地响应机械硬,以创建一个侵入性利基.
- 组织结构和性协同推动乳腺癌的进展.
- 揭示了Piezo1作为ECM重塑和入侵的调节者,以响应机械线索.
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