PMID- 27096955 OWN - NLM STAT- MEDLINE DCOM- 20171226 LR - 20211204 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 7 IP - 22 DP - 2016 May 31 TI - Fluid shear stress induces epithelial-mesenchymal transition (EMT) in Hep-2 cells. PG - 32876-92 LID - 10.18632/oncotarget.8765 [doi] AB - 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 beta-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. FAU - Liu, Shuangfeng AU - Liu S AD - Institute of Biomedical Engineering, School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China. AD - School of Medical Laboratory Science, Chengdu Medical College, Chengdu 610500, China. FAU - Zhou, Fating AU - Zhou F AD - Institute of Biomedical Engineering, School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China. FAU - Shen, Yang AU - Shen Y AD - Institute of Biomedical Engineering, School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China. FAU - Zhang, Yingying AU - Zhang Y AD - Institute of Biomedical Engineering, School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China. FAU - Yin, Hongmei AU - Yin H AD - West China School of Pharmacy, Sichuan University, Chengdu 610041, China. FAU - Zeng, Ye AU - Zeng Y AD - Institute of Biomedical Engineering, School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China. FAU - Liu, Jingxia AU - Liu J AD - Institute of Biomedical Engineering, School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China. FAU - Yan, Zhiping AU - Yan Z AD - Institute of Biomedical Engineering, School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China. FAU - Liu, Xiaoheng AU - Liu X AD - Institute of Biomedical Engineering, School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China. LA - eng PT - Journal Article PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 RN - 0 (Antigens, CD) RN - 0 (CDH1 protein, human) RN - 0 (CDH2 protein, human) RN - 0 (CTNNB1 protein, human) RN - 0 (Cadherins) RN - 0 (Snail Family Transcription Factors) RN - 0 (beta Catenin) RN - EC 2.7.1.- (integrin-linked kinase) RN - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Antigens, CD/metabolism MH - Cadherins/metabolism MH - Carcinoma, Squamous Cell/genetics/metabolism/*pathology MH - Cell Line, Tumor MH - Cell Movement MH - Cell Shape MH - *Epithelial-Mesenchymal Transition MH - Head and Neck Neoplasms/genetics/metabolism/*pathology MH - Humans MH - Laryngeal Neoplasms/genetics/metabolism/*pathology MH - *Mechanotransduction, Cellular MH - Phosphatidylinositol 3-Kinase/metabolism MH - Protein Serine-Threonine Kinases/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - Pseudopodia/metabolism/pathology MH - RNA Interference MH - Snail Family Transcription Factors/genetics/metabolism MH - Squamous Cell Carcinoma of Head and Neck MH - Stress, Mechanical MH - Time Factors MH - Transfection MH - Tumor Microenvironment MH - beta Catenin/metabolism PMC - PMC5078059 OTO - NOTNLM OT - cell migration OT - epithelial-mesenchymal transition (EMT) OT - fluid shear stress (FSS) OT - laryngeal squamous cell carcinomas (LSCC) COIS- The authors declare that have no conflicts of interest. EDAT- 2016/04/21 06:00 MHDA- 2017/12/27 06:00 PMCR- 2016/05/31 CRDT- 2016/04/21 06:00 PHST- 2015/07/21 00:00 [received] PHST- 2016/03/28 00:00 [accepted] PHST- 2016/04/21 06:00 [entrez] PHST- 2016/04/21 06:00 [pubmed] PHST- 2017/12/27 06:00 [medline] PHST- 2016/05/31 00:00 [pmc-release] AID - 8765 [pii] AID - 10.18632/oncotarget.8765 [doi] PST - ppublish SO - Oncotarget. 2016 May 31;7(22):32876-92. doi: 10.18632/oncotarget.8765.