Fluid shear stress induces epithelial-mesenchymal transition (EMT) in Hep-2 cells.
Fluid shear stress induces epithelial-mesenchymal transition (EMT) in Hep-2 cells.
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流体剪切应力诱导 Hep-2 细胞上皮间质转化 (EMT)
DOI：
10.18632/oncotarget.8765
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发表时间：
2016-05-31
期刊：
影响因子：
--
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Liu S;Zhou F;Shen Y;Zhang Y;Yin H;Zeng Y;Liu J;Yan Z;Liu X
喉鳞状细胞癌（LSCC）是最常见的恶性肿瘤之一，肿瘤转移发生率高，通常暴露在淋巴管和血管中的流体剪切应力（FSS）下。上皮间质转化（EMT）是诱导肿瘤转移和侵袭的重要机制。我们假设 FSS 诱导了喉鳞状细胞癌的 EMT 进展。因此，Hep-2 细胞暴露于 1.4 dyn/cm2 FSS 不同的持续时间。我们的结果表明，大多数细胞的形态从多边形转变为细长的纺锤体，具有组织良好的F-肌动蛋白和丰富的片状伪足/丝状伪足的突起。去除FSS后，细胞逐渐恢复其扁平多边形形态。 FSS诱导Hep-2细胞以时间依赖性方式增强其迁移能力。此外，FSS 下调 E-钙粘蛋白，同时上调 N-钙粘蛋白，将 β-连环蛋白易位到细胞核中。这些结果证实FSS诱导Hep-2细胞中的EMT，并揭示当FSS被去除时可逆的间充质-上皮转化（MET）过程。我们进一步检查了信号级联的时间表达，并证明 FSS 根据整合素-ILK/PI3K-AKT-Snail 信号事件诱导 EMT 并增强细胞迁移。目前的研究表明，FSS是肿瘤微环境中重要的生物物理因素，是细胞行为和功能调节的潜在决定因素。
Laryngeal squamous cell carcinoma (LSCC) is one of the most commonly diagnosed malignancies with high occurrence of tumor metastasis, which usually exposes to fluid shear stress (FSS) in lymphatic channel and blood vessel. Epithelial-mesenchymal transition (EMT) is an important mechanism that induces metastasis and invasion of tumors. We hypothesized that FSS induced a progression of EMT in laryngeal squamous carcinoma. Accordingly, the Hep-2 cells were exposed to 1.4 dyn/cm2 FSS for different durations. Our results showed that most of cells changed their morphology from polygon to elongated spindle with well-organized F-actin and abundant lamellipodia/filopodia in protrusions. After removing the FSS, cells gradually recovered their flat polygon morphology. FSS induced Hep-2 cells to enhance their migration capacity in a time-dependent manner. In addition, FSS down-regulated E-cadherin, and simultaneously up-regulated N-cadherin, translocated β-catenin into the nucleus. These results confirmed that FSS induced the EMT in Hep-2 cells, and revealed a reversible mesenchymal-epithelial transition (MET) process when FSS was removed. We further examined the time-expressions of signaling cascades, and demonstrated that FSS induces the EMT and enhances cell migration depending on integrin-ILK/PI3K-AKT-Snail signaling events. The current study suggests that FSS, an important biophysical factor in tumor microenvironment, is a potential determinant of cell behavior and function regulation.
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