Fluid shear stress induces epithelial-mesenchymal transition (EMT) in Hep-2 cells.
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.
Institute of Biomedical Engineering, School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China.|School of Medical Laboratory Science, Chengdu Medical College, Chengdu 610500, China.
Shuangfeng
S
Liu
Institute of Biomedical Engineering, School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China.
Fating
F
Zhou
Institute of Biomedical Engineering, School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China.
Yang
Y
Shen
Institute of Biomedical Engineering, School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China.
Yingying
Y
Zhang
West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Hongmei
H
Yin
Institute of Biomedical Engineering, School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China.
Ye
Y
Zeng
Institute of Biomedical Engineering, School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China.
Jingxia
J
Liu
Institute of Biomedical Engineering, School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China.
Zhiping
Z
Yan
Institute of Biomedical Engineering, School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China.
Xiaoheng
X
Liu
D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D048430:Cell Shape; D058750:Epithelial-Mesenchymal Transition; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D040542:Mechanotransduction, Cellular; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011554:Pseudopodia / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D000071250:Snail Family Transcription Factors / Q000235:genetics / Q000378:metabolism; D000077195:Squamous Cell Carcinoma of Head and Neck; D013314:Stress, Mechanical; D013997:Time Factors; D014162:Transfection; D059016:Tumor Microenvironment; D051176:beta Catenin / Q000378:metabolism; D000099200:Scaffold Protein ILK
D015703:Antigens, CD; D015820:Cadherins; D058539:Phosphatidylinositol 3-Kinase; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D000071250:Snail Family Transcription Factors; D051176:beta Catenin; D000099200:Scaffold Protein ILK; C513384:CDH1 protein, human; C050361:CDH2 protein, human; C495270:CTNNB1 protein, human
cell migration; epithelial-mesenchymal transition (EMT); fluid shear stress (FSS); laryngeal squamous cell carcinomas (LSCC)