Fractionated Ionizing Radiation Promotes Epithelial-Mesenchymal Transition in Human Esophageal Cancer Cells through PTEN Deficiency-Mediated Akt Activation
In some esophageal cancer patients, radiotherapy may not prevent distant metastasis thus resulting in poor survival. The underlying mechanism of metastasis in these patients is not well established. In this study, we have demonstrated that ionizing radiation may induce epithelial-mesenchymal transit...
Gespeichert in:
| Veröffentlicht in: | PloS one 2015-05, Vol.10 (5), p.e0126149-e0126149 |
|---|---|
| Hauptverfasser: | , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e0126149 |
|---|---|
| container_issue | 5 |
| container_start_page | e0126149 |
| container_title | PloS one |
| container_volume | 10 |
| creator | He, Enhui Pan, Fei Li, Guangchao Li, Jingjing |
| description | In some esophageal cancer patients, radiotherapy may not prevent distant metastasis thus resulting in poor survival. The underlying mechanism of metastasis in these patients is not well established. In this study, we have demonstrated that ionizing radiation may induce epithelial-mesenchymal transition (EMT) accompanied with increased cell migration and invasion, through downregulation of phosphatase and tensin homolog (PTEN), and activation of Akt/GSK-3β/Snail signaling. We developed a radioresistant (RR) esophageal squamous cancer cell line, KYSE-150/RR, by fractionated ionizing radiation (IR) treatment, and confirmed its radioresistance using a clonogenic survival assay. We found that the KYSE-150/RR cell line displayed typical morphological and molecular characteristics of EMT. In comparison to the parental cells, KYSE-150/RR cells showed an increase in post-IR colony survival, migration, and invasiveness. Furthermore, a decrease in PTEN in KYSE-150/RR cells was observed. We postulated that over-expression of PTEN may induce mesenchymal-epithelial transition in KYSE-150/RR cells and restore IR-induced increase of cell migration. Mechanistically, fractionated IR inhibits expression of PTEN, which leads to activation of Akt/GSK-3β signaling and is associated with the elevated levels of Snail protein, a transcription factor involved in EMT. Correspondingly, treatment with LY294002, a phosphatidylinositol-3-kinase inhibitor, mimicked PTEN overexpression effect in KYSE-150/RR cells, further suggesting a role for the Akt/GSK-3β/Snail signaling in effects mediated through PTEN. Together, these results strongly suggest that fractionated IR-mediated EMT in KYSE-150/RR cells is through PTEN-dependent pathways, highlighting a direct proinvasive effect of radiation treatment on tumor cells. |
| doi_str_mv | 10.1371/journal.pone.0126149 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1682657014</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A432322233</galeid><doaj_id>oai_doaj_org_article_8928cf2b78ac41f8ab3ccdadfa333337</doaj_id><sourcerecordid>A432322233</sourcerecordid><originalsourceid>FETCH-LOGICAL-c758t-54ecf365b45ebc7e7026b137885ba2a8eeeb2ba45f99a5af5d03c0db3752819d3</originalsourceid><addsrcrecordid>eNqNk99v0zAQxyMEYqPwHyCIhITgocWx88N5mVSVjlUabBqFV-viOIlLYhfbmSj_Cv8sTttNLdoD8UOs8-e-dz7fBcHLCE0ikkUfVro3CtrJWisxQRFOozh_FJxGOcHjFCPy-GB_EjyzdoVQQmiaPg1OcIoQohk9Df6cG-BOagVOlOFCK_lbqjq8gVLCYA6vje60Ezacr6VrRCuhHX8WVijebDpow6UBZeUWlSq86DtQ4dzqdQO18MczUFyYcCba1oauMbqvm_B6Of8SfhSV5NLrbLzeEM3Hn_5w4dSnc7uN_Tx4UkFrxYv9fxR8O58vZxfjy6tPi9n0csyzhLpxEgtekTQp4kQUPBMZwmnhS0RpUgAGKoQocAFxUuU5JFAlJSIclQXJEkyjvCSj4PVOd91qy_Z1tSxKKU6TDEWxJxY7otSwYmsjOzAbpkGyrUGbmoFxkreC0RxTXuEio8DjqKJQEM5LKCsgw5d5rbN9tL7oRMmFcgbaI9HjEyUbVutbFsdxRGjuBd7tBYz-2QvrWCct9wUGJXS_zZskWUxJ6tE3_6AP325P1eAvIFWlfVw-iLJpTDDBGPvMR8HkAcqvUnSS-yaspLcfObw_cvCME79cDb21bPH15v_Zq-_H7NsDtvFd5hqr235oGXsMxjuQG22tEdV9kSPEhhm6qwYbZojtZ8i7vTp8oHunu6EhfwF3LRmL</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1682657014</pqid></control><display><type>article</type><title>Fractionated Ionizing Radiation Promotes Epithelial-Mesenchymal Transition in Human Esophageal Cancer Cells through PTEN Deficiency-Mediated Akt Activation</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Public Library of Science (PLoS)</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>He, Enhui ; Pan, Fei ; Li, Guangchao ; Li, Jingjing</creator><creatorcontrib>He, Enhui ; Pan, Fei ; Li, Guangchao ; Li, Jingjing</creatorcontrib><description>In some esophageal cancer patients, radiotherapy may not prevent distant metastasis thus resulting in poor survival. The underlying mechanism of metastasis in these patients is not well established. In this study, we have demonstrated that ionizing radiation may induce epithelial-mesenchymal transition (EMT) accompanied with increased cell migration and invasion, through downregulation of phosphatase and tensin homolog (PTEN), and activation of Akt/GSK-3β/Snail signaling. We developed a radioresistant (RR) esophageal squamous cancer cell line, KYSE-150/RR, by fractionated ionizing radiation (IR) treatment, and confirmed its radioresistance using a clonogenic survival assay. We found that the KYSE-150/RR cell line displayed typical morphological and molecular characteristics of EMT. In comparison to the parental cells, KYSE-150/RR cells showed an increase in post-IR colony survival, migration, and invasiveness. Furthermore, a decrease in PTEN in KYSE-150/RR cells was observed. We postulated that over-expression of PTEN may induce mesenchymal-epithelial transition in KYSE-150/RR cells and restore IR-induced increase of cell migration. Mechanistically, fractionated IR inhibits expression of PTEN, which leads to activation of Akt/GSK-3β signaling and is associated with the elevated levels of Snail protein, a transcription factor involved in EMT. Correspondingly, treatment with LY294002, a phosphatidylinositol-3-kinase inhibitor, mimicked PTEN overexpression effect in KYSE-150/RR cells, further suggesting a role for the Akt/GSK-3β/Snail signaling in effects mediated through PTEN. Together, these results strongly suggest that fractionated IR-mediated EMT in KYSE-150/RR cells is through PTEN-dependent pathways, highlighting a direct proinvasive effect of radiation treatment on tumor cells.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0126149</identifier><identifier>PMID: 26000878</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>1-Phosphatidylinositol 3-kinase ; Activation ; AKT protein ; Analysis ; Apoptosis ; Cancer ; Carcinoma, Squamous Cell - metabolism ; Carcinoma, Squamous Cell - pathology ; Care and treatment ; Cell adhesion & migration ; Cell cycle ; Cell Line, Tumor ; Cell migration ; Cell Movement - radiation effects ; Cell survival ; Complications and side effects ; Development and progression ; Down-Regulation - radiation effects ; Drug dosages ; Enzyme inhibitors ; Epithelial-Mesenchymal Transition - radiation effects ; Esophageal cancer ; Esophageal Neoplasms - metabolism ; Esophageal Neoplasms - pathology ; Esophageal Squamous Cell Carcinoma ; Esophagus ; Genotype & phenotype ; Glycogen Synthase Kinase 3 - metabolism ; Glycogen Synthase Kinase 3 beta ; Homology ; Hospitals ; Humans ; I.R. radiation ; Invasiveness ; Ionizing radiation ; Kinases ; Lung cancer ; Mesenchyme ; Metastases ; Metastasis ; Mortality ; Overexpression ; Patient outcomes ; Patients ; Physical characteristics ; Physiological aspects ; Proto-Oncogene Proteins c-akt - metabolism ; PTEN Phosphohydrolase - genetics ; PTEN Phosphohydrolase - metabolism ; PTEN protein ; Radiation ; Radiation therapy ; Radiation, Ionizing ; Radioresistance ; Signal Transduction - radiation effects ; Signaling ; Snail protein ; Stem cells ; Survival ; Tensin ; Tumor cells</subject><ispartof>PloS one, 2015-05, Vol.10 (5), p.e0126149-e0126149</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 He et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 He et al 2015 He et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-54ecf365b45ebc7e7026b137885ba2a8eeeb2ba45f99a5af5d03c0db3752819d3</citedby><cites>FETCH-LOGICAL-c758t-54ecf365b45ebc7e7026b137885ba2a8eeeb2ba45f99a5af5d03c0db3752819d3</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/PMC4441389/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4441389/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,725,778,782,862,883,2098,2917,23849,27907,27908,53774,53776,79351,79352</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26000878$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>He, Enhui</creatorcontrib><creatorcontrib>Pan, Fei</creatorcontrib><creatorcontrib>Li, Guangchao</creatorcontrib><creatorcontrib>Li, Jingjing</creatorcontrib><title>Fractionated Ionizing Radiation Promotes Epithelial-Mesenchymal Transition in Human Esophageal Cancer Cells through PTEN Deficiency-Mediated Akt Activation</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>In some esophageal cancer patients, radiotherapy may not prevent distant metastasis thus resulting in poor survival. The underlying mechanism of metastasis in these patients is not well established. In this study, we have demonstrated that ionizing radiation may induce epithelial-mesenchymal transition (EMT) accompanied with increased cell migration and invasion, through downregulation of phosphatase and tensin homolog (PTEN), and activation of Akt/GSK-3β/Snail signaling. We developed a radioresistant (RR) esophageal squamous cancer cell line, KYSE-150/RR, by fractionated ionizing radiation (IR) treatment, and confirmed its radioresistance using a clonogenic survival assay. We found that the KYSE-150/RR cell line displayed typical morphological and molecular characteristics of EMT. In comparison to the parental cells, KYSE-150/RR cells showed an increase in post-IR colony survival, migration, and invasiveness. Furthermore, a decrease in PTEN in KYSE-150/RR cells was observed. We postulated that over-expression of PTEN may induce mesenchymal-epithelial transition in KYSE-150/RR cells and restore IR-induced increase of cell migration. Mechanistically, fractionated IR inhibits expression of PTEN, which leads to activation of Akt/GSK-3β signaling and is associated with the elevated levels of Snail protein, a transcription factor involved in EMT. Correspondingly, treatment with LY294002, a phosphatidylinositol-3-kinase inhibitor, mimicked PTEN overexpression effect in KYSE-150/RR cells, further suggesting a role for the Akt/GSK-3β/Snail signaling in effects mediated through PTEN. Together, these results strongly suggest that fractionated IR-mediated EMT in KYSE-150/RR cells is through PTEN-dependent pathways, highlighting a direct proinvasive effect of radiation treatment on tumor cells.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>Activation</subject><subject>AKT protein</subject><subject>Analysis</subject><subject>Apoptosis</subject><subject>Cancer</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Care and treatment</subject><subject>Cell adhesion & migration</subject><subject>Cell cycle</subject><subject>Cell Line, Tumor</subject><subject>Cell migration</subject><subject>Cell Movement - radiation effects</subject><subject>Cell survival</subject><subject>Complications and side effects</subject><subject>Development and progression</subject><subject>Down-Regulation - radiation effects</subject><subject>Drug dosages</subject><subject>Enzyme inhibitors</subject><subject>Epithelial-Mesenchymal Transition - radiation effects</subject><subject>Esophageal cancer</subject><subject>Esophageal Neoplasms - metabolism</subject><subject>Esophageal Neoplasms - pathology</subject><subject>Esophageal Squamous Cell Carcinoma</subject><subject>Esophagus</subject><subject>Genotype & phenotype</subject><subject>Glycogen Synthase Kinase 3 - metabolism</subject><subject>Glycogen Synthase Kinase 3 beta</subject><subject>Homology</subject><subject>Hospitals</subject><subject>Humans</subject><subject>I.R. radiation</subject><subject>Invasiveness</subject><subject>Ionizing radiation</subject><subject>Kinases</subject><subject>Lung cancer</subject><subject>Mesenchyme</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Mortality</subject><subject>Overexpression</subject><subject>Patient outcomes</subject><subject>Patients</subject><subject>Physical characteristics</subject><subject>Physiological aspects</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>PTEN Phosphohydrolase - genetics</subject><subject>PTEN Phosphohydrolase - metabolism</subject><subject>PTEN protein</subject><subject>Radiation</subject><subject>Radiation therapy</subject><subject>Radiation, Ionizing</subject><subject>Radioresistance</subject><subject>Signal Transduction - radiation effects</subject><subject>Signaling</subject><subject>Snail protein</subject><subject>Stem cells</subject><subject>Survival</subject><subject>Tensin</subject><subject>Tumor cells</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk99v0zAQxyMEYqPwHyCIhITgocWx88N5mVSVjlUabBqFV-viOIlLYhfbmSj_Cv8sTttNLdoD8UOs8-e-dz7fBcHLCE0ikkUfVro3CtrJWisxQRFOozh_FJxGOcHjFCPy-GB_EjyzdoVQQmiaPg1OcIoQohk9Df6cG-BOagVOlOFCK_lbqjq8gVLCYA6vje60Ezacr6VrRCuhHX8WVijebDpow6UBZeUWlSq86DtQ4dzqdQO18MczUFyYcCba1oauMbqvm_B6Of8SfhSV5NLrbLzeEM3Hn_5w4dSnc7uN_Tx4UkFrxYv9fxR8O58vZxfjy6tPi9n0csyzhLpxEgtekTQp4kQUPBMZwmnhS0RpUgAGKoQocAFxUuU5JFAlJSIclQXJEkyjvCSj4PVOd91qy_Z1tSxKKU6TDEWxJxY7otSwYmsjOzAbpkGyrUGbmoFxkreC0RxTXuEio8DjqKJQEM5LKCsgw5d5rbN9tL7oRMmFcgbaI9HjEyUbVutbFsdxRGjuBd7tBYz-2QvrWCct9wUGJXS_zZskWUxJ6tE3_6AP325P1eAvIFWlfVw-iLJpTDDBGPvMR8HkAcqvUnSS-yaspLcfObw_cvCME79cDb21bPH15v_Zq-_H7NsDtvFd5hqr235oGXsMxjuQG22tEdV9kSPEhhm6qwYbZojtZ8i7vTp8oHunu6EhfwF3LRmL</recordid><startdate>20150522</startdate><enddate>20150522</enddate><creator>He, Enhui</creator><creator>Pan, Fei</creator><creator>Li, Guangchao</creator><creator>Li, Jingjing</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150522</creationdate><title>Fractionated Ionizing Radiation Promotes Epithelial-Mesenchymal Transition in Human Esophageal Cancer Cells through PTEN Deficiency-Mediated Akt Activation</title><author>He, Enhui ; Pan, Fei ; Li, Guangchao ; Li, Jingjing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-54ecf365b45ebc7e7026b137885ba2a8eeeb2ba45f99a5af5d03c0db3752819d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>Activation</topic><topic>AKT protein</topic><topic>Analysis</topic><topic>Apoptosis</topic><topic>Cancer</topic><topic>Carcinoma, Squamous Cell - metabolism</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>Care and treatment</topic><topic>Cell adhesion & migration</topic><topic>Cell cycle</topic><topic>Cell Line, Tumor</topic><topic>Cell migration</topic><topic>Cell Movement - radiation effects</topic><topic>Cell survival</topic><topic>Complications and side effects</topic><topic>Development and progression</topic><topic>Down-Regulation - radiation effects</topic><topic>Drug dosages</topic><topic>Enzyme inhibitors</topic><topic>Epithelial-Mesenchymal Transition - radiation effects</topic><topic>Esophageal cancer</topic><topic>Esophageal Neoplasms - metabolism</topic><topic>Esophageal Neoplasms - pathology</topic><topic>Esophageal Squamous Cell Carcinoma</topic><topic>Esophagus</topic><topic>Genotype & phenotype</topic><topic>Glycogen Synthase Kinase 3 - metabolism</topic><topic>Glycogen Synthase Kinase 3 beta</topic><topic>Homology</topic><topic>Hospitals</topic><topic>Humans</topic><topic>I.R. radiation</topic><topic>Invasiveness</topic><topic>Ionizing radiation</topic><topic>Kinases</topic><topic>Lung cancer</topic><topic>Mesenchyme</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Mortality</topic><topic>Overexpression</topic><topic>Patient outcomes</topic><topic>Patients</topic><topic>Physical characteristics</topic><topic>Physiological aspects</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>PTEN Phosphohydrolase - genetics</topic><topic>PTEN Phosphohydrolase - metabolism</topic><topic>PTEN protein</topic><topic>Radiation</topic><topic>Radiation therapy</topic><topic>Radiation, Ionizing</topic><topic>Radioresistance</topic><topic>Signal Transduction - radiation effects</topic><topic>Signaling</topic><topic>Snail protein</topic><topic>Stem cells</topic><topic>Survival</topic><topic>Tensin</topic><topic>Tumor cells</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>He, Enhui</creatorcontrib><creatorcontrib>Pan, Fei</creatorcontrib><creatorcontrib>Li, Guangchao</creatorcontrib><creatorcontrib>Li, Jingjing</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection (ProQuest)</collection><collection>Natural Science Collection (ProQuest)</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>He, Enhui</au><au>Pan, Fei</au><au>Li, Guangchao</au><au>Li, Jingjing</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fractionated Ionizing Radiation Promotes Epithelial-Mesenchymal Transition in Human Esophageal Cancer Cells through PTEN Deficiency-Mediated Akt Activation</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-05-22</date><risdate>2015</risdate><volume>10</volume><issue>5</issue><spage>e0126149</spage><epage>e0126149</epage><pages>e0126149-e0126149</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>In some esophageal cancer patients, radiotherapy may not prevent distant metastasis thus resulting in poor survival. The underlying mechanism of metastasis in these patients is not well established. In this study, we have demonstrated that ionizing radiation may induce epithelial-mesenchymal transition (EMT) accompanied with increased cell migration and invasion, through downregulation of phosphatase and tensin homolog (PTEN), and activation of Akt/GSK-3β/Snail signaling. We developed a radioresistant (RR) esophageal squamous cancer cell line, KYSE-150/RR, by fractionated ionizing radiation (IR) treatment, and confirmed its radioresistance using a clonogenic survival assay. We found that the KYSE-150/RR cell line displayed typical morphological and molecular characteristics of EMT. In comparison to the parental cells, KYSE-150/RR cells showed an increase in post-IR colony survival, migration, and invasiveness. Furthermore, a decrease in PTEN in KYSE-150/RR cells was observed. We postulated that over-expression of PTEN may induce mesenchymal-epithelial transition in KYSE-150/RR cells and restore IR-induced increase of cell migration. Mechanistically, fractionated IR inhibits expression of PTEN, which leads to activation of Akt/GSK-3β signaling and is associated with the elevated levels of Snail protein, a transcription factor involved in EMT. Correspondingly, treatment with LY294002, a phosphatidylinositol-3-kinase inhibitor, mimicked PTEN overexpression effect in KYSE-150/RR cells, further suggesting a role for the Akt/GSK-3β/Snail signaling in effects mediated through PTEN. Together, these results strongly suggest that fractionated IR-mediated EMT in KYSE-150/RR cells is through PTEN-dependent pathways, highlighting a direct proinvasive effect of radiation treatment on tumor cells.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26000878</pmid><doi>10.1371/journal.pone.0126149</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2015-05, Vol.10 (5), p.e0126149-e0126149 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1682657014 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 1-Phosphatidylinositol 3-kinase Activation AKT protein Analysis Apoptosis Cancer Carcinoma, Squamous Cell - metabolism Carcinoma, Squamous Cell - pathology Care and treatment Cell adhesion & migration Cell cycle Cell Line, Tumor Cell migration Cell Movement - radiation effects Cell survival Complications and side effects Development and progression Down-Regulation - radiation effects Drug dosages Enzyme inhibitors Epithelial-Mesenchymal Transition - radiation effects Esophageal cancer Esophageal Neoplasms - metabolism Esophageal Neoplasms - pathology Esophageal Squamous Cell Carcinoma Esophagus Genotype & phenotype Glycogen Synthase Kinase 3 - metabolism Glycogen Synthase Kinase 3 beta Homology Hospitals Humans I.R. radiation Invasiveness Ionizing radiation Kinases Lung cancer Mesenchyme Metastases Metastasis Mortality Overexpression Patient outcomes Patients Physical characteristics Physiological aspects Proto-Oncogene Proteins c-akt - metabolism PTEN Phosphohydrolase - genetics PTEN Phosphohydrolase - metabolism PTEN protein Radiation Radiation therapy Radiation, Ionizing Radioresistance Signal Transduction - radiation effects Signaling Snail protein Stem cells Survival Tensin Tumor cells |
| title | Fractionated Ionizing Radiation Promotes Epithelial-Mesenchymal Transition in Human Esophageal Cancer Cells through PTEN Deficiency-Mediated Akt Activation |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-16T08%3A29%3A34IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Fractionated%20Ionizing%20Radiation%20Promotes%20Epithelial-Mesenchymal%20Transition%20in%20Human%20Esophageal%20Cancer%20Cells%20through%20PTEN%20Deficiency-Mediated%20Akt%20Activation&rft.jtitle=PloS%20one&rft.au=He,%20Enhui&rft.date=2015-05-22&rft.volume=10&rft.issue=5&rft.spage=e0126149&rft.epage=e0126149&rft.pages=e0126149-e0126149&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0126149&rft_dat=%3Cgale_plos_%3EA432322233%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1682657014&rft_id=info:pmid/26000878&rft_galeid=A432322233&rft_doaj_id=oai_doaj_org_article_8928cf2b78ac41f8ab3ccdadfa333337&rfr_iscdi=true |