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 induce...

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Veröffentlicht in:Oncotarget 2016-05, Vol.7 (22), p.32876-32892
Hauptverfasser: Liu, Shuangfeng, Zhou, Fating, Shen, Yang, Zhang, Yingying, Yin, Hongmei, Zeng, Ye, Liu, Jingxia, Yan, Zhiping, Liu, Xiaoheng
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container_issue 22
container_start_page 32876
container_title Oncotarget
container_volume 7
creator Liu, Shuangfeng
Zhou, Fating
Shen, Yang
Zhang, Yingying
Yin, Hongmei
Zeng, Ye
Liu, Jingxia
Yan, Zhiping
Liu, Xiaoheng
description 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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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.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.8765</identifier><identifier>PMID: 27096955</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>Antigens, CD - metabolism ; beta Catenin - metabolism ; Cadherins - metabolism ; Carcinoma, Squamous Cell - genetics ; Carcinoma, Squamous Cell - metabolism ; Carcinoma, Squamous Cell - pathology ; Cell Line, Tumor ; Cell Movement ; Cell Shape ; Epithelial-Mesenchymal Transition ; Head and Neck Neoplasms - genetics ; Head and Neck Neoplasms - metabolism ; Head and Neck Neoplasms - pathology ; Humans ; Laryngeal Neoplasms - genetics ; Laryngeal Neoplasms - metabolism ; Laryngeal Neoplasms - pathology ; Mechanotransduction, Cellular ; Phosphatidylinositol 3-Kinase - metabolism ; Protein-Serine-Threonine Kinases - metabolism ; Proto-Oncogene Proteins c-akt - metabolism ; Pseudopodia - metabolism ; Pseudopodia - pathology ; Research Paper ; RNA Interference ; Snail Family Transcription Factors - genetics ; Snail Family Transcription Factors - metabolism ; Squamous Cell Carcinoma of Head and Neck ; Stress, Mechanical ; Time Factors ; Transfection ; Tumor Microenvironment</subject><ispartof>Oncotarget, 2016-05, Vol.7 (22), p.32876-32892</ispartof><rights>Copyright: © 2016 Liu et al. 2016</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c354t-c30a27daa49a34b1dbbe14ef90ff9af437f5b5e966c725a827db40fc41b9701f3</citedby><cites>FETCH-LOGICAL-c354t-c30a27daa49a34b1dbbe14ef90ff9af437f5b5e966c725a827db40fc41b9701f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5078059/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5078059/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27096955$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Shuangfeng</creatorcontrib><creatorcontrib>Zhou, Fating</creatorcontrib><creatorcontrib>Shen, Yang</creatorcontrib><creatorcontrib>Zhang, Yingying</creatorcontrib><creatorcontrib>Yin, Hongmei</creatorcontrib><creatorcontrib>Zeng, Ye</creatorcontrib><creatorcontrib>Liu, Jingxia</creatorcontrib><creatorcontrib>Yan, Zhiping</creatorcontrib><creatorcontrib>Liu, Xiaoheng</creatorcontrib><title>Fluid shear stress induces epithelial-mesenchymal transition (EMT) in Hep-2 cells</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>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. 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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.</description><subject>Antigens, CD - metabolism</subject><subject>beta Catenin - metabolism</subject><subject>Cadherins - metabolism</subject><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement</subject><subject>Cell Shape</subject><subject>Epithelial-Mesenchymal Transition</subject><subject>Head and Neck Neoplasms - genetics</subject><subject>Head and Neck Neoplasms - metabolism</subject><subject>Head and Neck Neoplasms - pathology</subject><subject>Humans</subject><subject>Laryngeal Neoplasms - genetics</subject><subject>Laryngeal Neoplasms - metabolism</subject><subject>Laryngeal Neoplasms - pathology</subject><subject>Mechanotransduction, Cellular</subject><subject>Phosphatidylinositol 3-Kinase - metabolism</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Pseudopodia - metabolism</subject><subject>Pseudopodia - pathology</subject><subject>Research Paper</subject><subject>RNA Interference</subject><subject>Snail Family Transcription Factors - genetics</subject><subject>Snail Family Transcription Factors - metabolism</subject><subject>Squamous Cell Carcinoma of Head and Neck</subject><subject>Stress, Mechanical</subject><subject>Time Factors</subject><subject>Transfection</subject><subject>Tumor Microenvironment</subject><issn>1949-2553</issn><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkd9LwzAQx4Mobsy9-yR9nA-dSZq0zYsgwzlhIsJ8Dml6WSP9MZNW2H9v5-ac95A7yOe-d8kXoWuCpySNI3rX1LpplVtDO02TmJ-hIRFMhJTz6PykHqCx9x-4D86SlIpLNKAJFrHgfIje5mVn88AXoFzgWwfeB7bOOw0-gI1tCyitKsMKPNS62FaqDFqnam9b29TB5PFlddvzwQI2IQ00lKW_QhdGlR7GhzxC7_PH1WwRLl-fnmcPy1BHnLX9iRVNcqWYUBHLSJ5lQBgYgY0RyrAoMTzjIOJYJ5SrtGczho1mJBMJJiYaofu97qbLKsg11P1ipdw4Wym3lY2y8v9NbQu5br4kx0mKuegFJgcB13x24FtZWb97gqqh6bwkKd1hMaE9iveodo33DsxxDMHyxwz5Z4bcmdG33Jyud2z4_froG5lPieU</recordid><startdate>20160531</startdate><enddate>20160531</enddate><creator>Liu, Shuangfeng</creator><creator>Zhou, Fating</creator><creator>Shen, Yang</creator><creator>Zhang, Yingying</creator><creator>Yin, Hongmei</creator><creator>Zeng, Ye</creator><creator>Liu, Jingxia</creator><creator>Yan, Zhiping</creator><creator>Liu, Xiaoheng</creator><general>Impact Journals LLC</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20160531</creationdate><title>Fluid shear stress induces epithelial-mesenchymal transition (EMT) in Hep-2 cells</title><author>Liu, Shuangfeng ; 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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.</abstract><cop>United States</cop><pub>Impact Journals LLC</pub><pmid>27096955</pmid><doi>10.18632/oncotarget.8765</doi><tpages>17</tpages><oa>free_for_read</oa></addata></record>
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subjects Antigens, CD - metabolism
beta Catenin - metabolism
Cadherins - metabolism
Carcinoma, Squamous Cell - genetics
Carcinoma, Squamous Cell - metabolism
Carcinoma, Squamous Cell - pathology
Cell Line, Tumor
Cell Movement
Cell Shape
Epithelial-Mesenchymal Transition
Head and Neck Neoplasms - genetics
Head and Neck Neoplasms - metabolism
Head and Neck Neoplasms - pathology
Humans
Laryngeal Neoplasms - genetics
Laryngeal Neoplasms - metabolism
Laryngeal Neoplasms - pathology
Mechanotransduction, Cellular
Phosphatidylinositol 3-Kinase - metabolism
Protein-Serine-Threonine Kinases - metabolism
Proto-Oncogene Proteins c-akt - metabolism
Pseudopodia - metabolism
Pseudopodia - pathology
Research Paper
RNA Interference
Snail Family Transcription Factors - genetics
Snail Family Transcription Factors - metabolism
Squamous Cell Carcinoma of Head and Neck
Stress, Mechanical
Time Factors
Transfection
Tumor Microenvironment
title Fluid shear stress induces epithelial-mesenchymal transition (EMT) in Hep-2 cells
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