毛细管收缩通过PIEZO1产生主要癌细胞的瘤性
Giulia Silvani1, Chantal Kopecky2, Sara Romanazzo2
1School of Materials Science and Engineering, UNSW, Sydney, NSW, Australia.
Nature communications
|September 1, 2025
概括
通过狭窄的毛细血管挤压循环的黑色素瘤细胞, 这种由PIEZO1介导的机械应力增强了它们的转移潜力和形成二次瘤的能力.
科学领域:
- 癌症学
- 细胞生物学
- 生物物理
背景情况:
- 大多数癌症死亡的原因是转移.
- 只有很少的循环瘤细胞 (CTC) 形成二次瘤,这表明适应机制对于传播至关重要.
- 了解CTC在循环过程中如何适应是预防转移的关键.
研究的目的:
- 研究微毛细管穿越过程中机械力量对循环黑色素瘤细胞的影响.
- 找出参与这种机械重编程的细胞机制和分子途径.
- 确定这种重编程是否增强了黑色素瘤细胞的瘤和转移潜力.
主要方法:
- 使用微流体装置模拟生理流量和毛细血管缩小.
- 分析细胞和核变形,染色体重塑和信号 (PIEZO1).
- 评估基因表达的变化,干细胞标志物上调,跨内皮侵袭以及体外和体内瘤性.
主要成果:
- 微毛囊收缩诱导了细胞和核的快速变形,通过PIEZO1进行染色体重塑和信号传递.
- 收缩导致代谢重编程和转移过程的转录升高.
- 被挤压的细胞采用了类似于癌症干细胞的稳定状态,呈现出增加的黑色素瘤干细胞标志物,增强的侵入性和更大的瘤性.
- PIEZO1 抑制阻断了转变,而 PIEZO1 激活诱导了转变; PIEZO1 删除取消了受收缩诱导的表型.
结论:
- 在微毛细管过渡过程中经历的压缩力将循环黑色素瘤细胞重新编程成类似癌症干细胞的瘤原生状态.
- 机械传感器PIEZO1对于调解这种强力诱导的细胞重编程至关重要.
- 这些发现揭示了一种新的机制,即机械应力促使癌细胞扩散和转移殖民.
更多相关视频
07:41Three-dimensional Cell Culture Model for Measuring the Effects of Interstitial Fluid Flow on Tumor Cell Invasion
Published on: July 25, 2012
16.8K
08:51A Real-time Electrical Impedance Based Technique to Measure Invasion of Endothelial Cell Monolayer by Cancer Cells
Published on: April 1, 2011
27.4K
相关概念视频
Cell-matrix's Response to Mechanical Forces
2.7K
In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue.
Anchoring junctions mechanically attach a cell to the...
Anchoring junctions mechanically attach a cell to the...
2.7K
Cancer Cell Migration through Invadopodia
2.4K
Invadosome is a broad category of cell surface structures with proteolytic activity that degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
2.4K
Regulation of Angiogenesis and Blood Supply
2.7K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.7K
Overview of Cell-Matrix Interactions
7.5K
The extracellular matrix or ECM holds cells together to form a tissue and allows the cells within the tissue to communicate. ECM comprises proteins such as fibronectin, collagen, laminin, etc. The most abundant protein in this space is collagen. Collagen fibers are interwoven with carbohydrate-containing protein molecules called proteoglycans. ECM allows cell migration and provides a structural scaffold at cell adhesion that anchors the cell when the extracellular matrix proteins interact with...
7.5K
Interactions Between Signaling Pathways
6.4K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.4K
mTOR Signaling and Cancer Progression
3.9K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.9K
