Fluid shear stress induces epithelial-mesenchymal transition (EMT) in Hep-2 cells
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Shuangfeng Liu1,3,*, Fating Zhou1,*, Yang Shen1, Yingying Zhang1, Hongmei Yin2, Ye Zeng1, Jingxia Liu1, Zhiping Yan1, Xiaoheng Liu1
1Institute of Biomedical Engineering, School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China
2West China School of Pharmacy, Sichuan University, Chengdu 610041, China
3School of Medical Laboratory Science, Chengdu Medical College, Chengdu 610500, China
*These authors contributed equally to this work
Xiaoheng Liu, email: [email protected]
Keywords: fluid shear stress (FSS), epithelial-mesenchymal transition (EMT), laryngeal squamous cell carcinomas (LSCC), cell migration
Received: July 21, 2015 Accepted: March 28, 2016 Published: April 16, 2016
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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