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TWIST1 a new determinant of epithelial to mesenchymal transition in EGFR mutated lung adenocarcinoma
Metastasis is a multistep process and the main cause of mortality in lung cancer patients. We previously showed that EGFR mutations were associated with a copy number gain at a locus encompassing the TWIST1 gene on chromosome 7. TWIST1 is a highly conserved developmental gene involved in embryogenes...
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Published in: | PloS one 2012-01, Vol.7 (1), p.e29954-e29954 |
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creator | Pallier, Karine Cessot, Anatole Côté, Jean-Francois Just, Pierre-Alexandre Cazes, Aurélie Fabre, Elizabeth Danel, Claire Riquet, Marc Devouassoux-Shisheboran, Mojgan Ansieau, Stéphane Puisieux, Alain Laurent-Puig, Pierre Blons, Hélène |
description | Metastasis is a multistep process and the main cause of mortality in lung cancer patients. We previously showed that EGFR mutations were associated with a copy number gain at a locus encompassing the TWIST1 gene on chromosome 7. TWIST1 is a highly conserved developmental gene involved in embryogenesis that may be reactivated in cancers promoting both malignant conversion and cancer progression through an epithelial to mesenchymal transition (EMT). The aim of this study was to investigate the possible implication of TWIST1 reactivation on the acquisition of a mesenchymal phenotype in EGFR mutated lung cancer. We studied a series of consecutive lung adenocarcinoma from Caucasian non-smokers for which surgical frozen samples were available (n = 33) and showed that TWIST1 expression was linked to EGFR mutations (P |
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We previously showed that EGFR mutations were associated with a copy number gain at a locus encompassing the TWIST1 gene on chromosome 7. TWIST1 is a highly conserved developmental gene involved in embryogenesis that may be reactivated in cancers promoting both malignant conversion and cancer progression through an epithelial to mesenchymal transition (EMT). The aim of this study was to investigate the possible implication of TWIST1 reactivation on the acquisition of a mesenchymal phenotype in EGFR mutated lung cancer. We studied a series of consecutive lung adenocarcinoma from Caucasian non-smokers for which surgical frozen samples were available (n = 33) and showed that TWIST1 expression was linked to EGFR mutations (P<0.001), to low CDH1 expression (P<0.05) and low disease free survival (P = 0.044). To validate that TWIST1 is a driver of EMT in EGFR mutated lung cancer, we used five human lung cancer cell lines and demonstrated that EMT and the associated cell mobility were dependent upon TWIST1 expression in cells with EGFR mutation. Moreover a decrease of EGFR pathway stimulation through EGF retrieval or an inhibition of TWIST1 expression by small RNA technology reversed the phenomenon. Collectively, our in vivo and in vitro findings support that TWIST1 collaborates with the EGF pathway in promoting EMT in EGFR mutated lung adenocarcinoma and that large series of EGFR mutated lung cancer patients are needed to further define the prognostic role of TWIST1 reactivation in this subgroup.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0029954</identifier><identifier>PMID: 22272264</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Activation ; Adenocarcinoma ; Adenocarcinoma - genetics ; Adenocarcinoma - metabolism ; Adenocarcinoma - pathology ; Aged ; Aged, 80 and over ; Antigens, CD - genetics ; Antigens, CD - metabolism ; Biology ; Blotting, Western ; Cadherins - genetics ; Cadherins - metabolism ; Cancer ; Cell growth ; Cell Line, Tumor ; Cell Movement - genetics ; Chromosome 7 ; Cooperation ; Copy number ; Development and progression ; E-cadherin ; Embryogenesis ; Embryonic growth stage ; Epidermal growth factor ; Epidermal Growth Factor - pharmacology ; Epidermal growth factor receptors ; Epidermal growth factors ; Epithelial-Mesenchymal Transition - drug effects ; Epithelial-Mesenchymal Transition - genetics ; Female ; Gene expression ; Gene Expression Regulation, Neoplastic ; Genetic aspects ; Head & neck cancer ; Health aspects ; Humans ; Hypoxia ; Immunohistochemistry ; Kaplan-Meier Estimate ; Kinases ; Lung cancer ; Lung diseases ; Lung Neoplasms - genetics ; Lung Neoplasms - metabolism ; Lung Neoplasms - pathology ; Male ; Medicine ; Mesenchyme ; Metastases ; Metastasis ; Middle Aged ; Mortality ; Motility ; Mutation ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; Pathology ; Patients ; Receptor, Epidermal Growth Factor - genetics ; Receptor, Epidermal Growth Factor - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Ribonucleic acid ; RNA ; RNA Interference ; Senescence ; Smoking ; Stem cells ; Surgery ; Thoracic surgery ; Tumor cell lines ; Tumors ; Twist-Related Protein 1 - genetics ; Twist-Related Protein 1 - metabolism</subject><ispartof>PloS one, 2012-01, Vol.7 (1), p.e29954-e29954</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Pallier et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://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>Pallier et al. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c757t-ba8b0383330cd3ecdb6c3924e6243b8c7af784a37986ebfd47d1b265e753fd093</citedby><cites>FETCH-LOGICAL-c757t-ba8b0383330cd3ecdb6c3924e6243b8c7af784a37986ebfd47d1b265e753fd093</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1323077581/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1323077581?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25752,27923,27924,37011,37012,44589,53790,53792,74897</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22272264$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Klymkowsky, Michael</contributor><creatorcontrib>Pallier, Karine</creatorcontrib><creatorcontrib>Cessot, Anatole</creatorcontrib><creatorcontrib>Côté, Jean-Francois</creatorcontrib><creatorcontrib>Just, Pierre-Alexandre</creatorcontrib><creatorcontrib>Cazes, Aurélie</creatorcontrib><creatorcontrib>Fabre, Elizabeth</creatorcontrib><creatorcontrib>Danel, Claire</creatorcontrib><creatorcontrib>Riquet, Marc</creatorcontrib><creatorcontrib>Devouassoux-Shisheboran, Mojgan</creatorcontrib><creatorcontrib>Ansieau, Stéphane</creatorcontrib><creatorcontrib>Puisieux, Alain</creatorcontrib><creatorcontrib>Laurent-Puig, Pierre</creatorcontrib><creatorcontrib>Blons, Hélène</creatorcontrib><title>TWIST1 a new determinant of epithelial to mesenchymal transition in EGFR mutated lung adenocarcinoma</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Metastasis is a multistep process and the main cause of mortality in lung cancer patients. We previously showed that EGFR mutations were associated with a copy number gain at a locus encompassing the TWIST1 gene on chromosome 7. TWIST1 is a highly conserved developmental gene involved in embryogenesis that may be reactivated in cancers promoting both malignant conversion and cancer progression through an epithelial to mesenchymal transition (EMT). The aim of this study was to investigate the possible implication of TWIST1 reactivation on the acquisition of a mesenchymal phenotype in EGFR mutated lung cancer. We studied a series of consecutive lung adenocarcinoma from Caucasian non-smokers for which surgical frozen samples were available (n = 33) and showed that TWIST1 expression was linked to EGFR mutations (P<0.001), to low CDH1 expression (P<0.05) and low disease free survival (P = 0.044). To validate that TWIST1 is a driver of EMT in EGFR mutated lung cancer, we used five human lung cancer cell lines and demonstrated that EMT and the associated cell mobility were dependent upon TWIST1 expression in cells with EGFR mutation. Moreover a decrease of EGFR pathway stimulation through EGF retrieval or an inhibition of TWIST1 expression by small RNA technology reversed the phenomenon. Collectively, our in vivo and in vitro findings support that TWIST1 collaborates with the EGF pathway in promoting EMT in EGFR mutated lung adenocarcinoma and that large series of EGFR mutated lung cancer patients are needed to further define the prognostic role of TWIST1 reactivation in this subgroup.</description><subject>Activation</subject><subject>Adenocarcinoma</subject><subject>Adenocarcinoma - genetics</subject><subject>Adenocarcinoma - metabolism</subject><subject>Adenocarcinoma - pathology</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antigens, CD - genetics</subject><subject>Antigens, CD - metabolism</subject><subject>Biology</subject><subject>Blotting, Western</subject><subject>Cadherins - genetics</subject><subject>Cadherins - metabolism</subject><subject>Cancer</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - genetics</subject><subject>Chromosome 7</subject><subject>Cooperation</subject><subject>Copy number</subject><subject>Development and progression</subject><subject>E-cadherin</subject><subject>Embryogenesis</subject><subject>Embryonic growth stage</subject><subject>Epidermal growth factor</subject><subject>Epidermal Growth Factor - pharmacology</subject><subject>Epidermal growth factor receptors</subject><subject>Epidermal growth factors</subject><subject>Epithelial-Mesenchymal Transition - drug effects</subject><subject>Epithelial-Mesenchymal Transition - genetics</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genetic aspects</subject><subject>Head & neck cancer</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Immunohistochemistry</subject><subject>Kaplan-Meier Estimate</subject><subject>Kinases</subject><subject>Lung cancer</subject><subject>Lung diseases</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - metabolism</subject><subject>Lung Neoplasms - pathology</subject><subject>Male</subject><subject>Medicine</subject><subject>Mesenchyme</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Motility</subject><subject>Mutation</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>Pathology</subject><subject>Patients</subject><subject>Receptor, Epidermal Growth Factor - genetics</subject><subject>Receptor, Epidermal Growth Factor - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA Interference</subject><subject>Senescence</subject><subject>Smoking</subject><subject>Stem cells</subject><subject>Surgery</subject><subject>Thoracic surgery</subject><subject>Tumor cell lines</subject><subject>Tumors</subject><subject>Twist-Related Protein 1 - genetics</subject><subject>Twist-Related Protein 1 - metabolism</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNqNk99v0zAQxyMEYmPwHyCwhATiocXxz-QFaZq2UWnSpK3Ao-XYl9ZVYpfYAfbfk9BsatEekB9snz_3Pft8l2WvczzPqcw_bULfed3Mt8HDHGNSlpw9yY7zkpKZIJg-3VsfZS9i3GDMaSHE8-yIECIJEew4s8vvi9tljjTy8AtZSNC1zmufUKgRbF1aQ-N0g1JALUTwZn3XjttO--iSCx45j84vL25Q2yedwKKm9yukLfhgdGecD61-mT2rdRPh1TSfZF8vzpdnX2ZX15eLs9OrmZFcplmliwrTglKKjaVgbCUMLQkDQRitCiN1LQumqSwLAVVtmbR5RQQHyWltcUlPsrc73W0TopoSFFVOCcVS8iIfiMWOsEFv1LZzre7uVNBO_TWEbqV0l5xpQGFLtYFKg7CWMWGrgnNeMgu2LgindtD6PEXrqxasAT9kpTkQPTzxbq1W4aeiROC8kIPAh0mgCz96iEm1LhpoGu0h9FGVuSy44FIM5Lt_yMcfN1ErPdzf-ToMYc2oqU6ZlFhyVo5R549Qw7DQOjMUU-0G-4HDxwOHgUnwO610H6Na3N78P3v97ZB9v8euQTdpHUPTj1UVD0G2A00XYuygfshxjtXYC_fZUGMvqKkXBrc3-__z4HRf_PQPGOME2A</recordid><startdate>20120117</startdate><enddate>20120117</enddate><creator>Pallier, Karine</creator><creator>Cessot, Anatole</creator><creator>Côté, Jean-Francois</creator><creator>Just, Pierre-Alexandre</creator><creator>Cazes, Aurélie</creator><creator>Fabre, Elizabeth</creator><creator>Danel, Claire</creator><creator>Riquet, Marc</creator><creator>Devouassoux-Shisheboran, Mojgan</creator><creator>Ansieau, Stéphane</creator><creator>Puisieux, Alain</creator><creator>Laurent-Puig, Pierre</creator><creator>Blons, Hélène</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>20120117</creationdate><title>TWIST1 a new determinant of epithelial to mesenchymal transition in EGFR mutated lung adenocarcinoma</title><author>Pallier, Karine ; Cessot, Anatole ; Côté, Jean-Francois ; Just, Pierre-Alexandre ; Cazes, Aurélie ; Fabre, Elizabeth ; Danel, Claire ; Riquet, Marc ; Devouassoux-Shisheboran, Mojgan ; Ansieau, Stéphane ; Puisieux, Alain ; Laurent-Puig, Pierre ; Blons, Hélène</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c757t-ba8b0383330cd3ecdb6c3924e6243b8c7af784a37986ebfd47d1b265e753fd093</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Activation</topic><topic>Adenocarcinoma</topic><topic>Adenocarcinoma - 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Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agriculture 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 (ProQuest)</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>Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pallier, Karine</au><au>Cessot, Anatole</au><au>Côté, Jean-Francois</au><au>Just, Pierre-Alexandre</au><au>Cazes, Aurélie</au><au>Fabre, Elizabeth</au><au>Danel, Claire</au><au>Riquet, Marc</au><au>Devouassoux-Shisheboran, Mojgan</au><au>Ansieau, Stéphane</au><au>Puisieux, Alain</au><au>Laurent-Puig, Pierre</au><au>Blons, Hélène</au><au>Klymkowsky, Michael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>TWIST1 a new determinant of epithelial to mesenchymal transition in EGFR mutated lung adenocarcinoma</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-01-17</date><risdate>2012</risdate><volume>7</volume><issue>1</issue><spage>e29954</spage><epage>e29954</epage><pages>e29954-e29954</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Metastasis is a multistep process and the main cause of mortality in lung cancer patients. We previously showed that EGFR mutations were associated with a copy number gain at a locus encompassing the TWIST1 gene on chromosome 7. TWIST1 is a highly conserved developmental gene involved in embryogenesis that may be reactivated in cancers promoting both malignant conversion and cancer progression through an epithelial to mesenchymal transition (EMT). The aim of this study was to investigate the possible implication of TWIST1 reactivation on the acquisition of a mesenchymal phenotype in EGFR mutated lung cancer. We studied a series of consecutive lung adenocarcinoma from Caucasian non-smokers for which surgical frozen samples were available (n = 33) and showed that TWIST1 expression was linked to EGFR mutations (P<0.001), to low CDH1 expression (P<0.05) and low disease free survival (P = 0.044). To validate that TWIST1 is a driver of EMT in EGFR mutated lung cancer, we used five human lung cancer cell lines and demonstrated that EMT and the associated cell mobility were dependent upon TWIST1 expression in cells with EGFR mutation. Moreover a decrease of EGFR pathway stimulation through EGF retrieval or an inhibition of TWIST1 expression by small RNA technology reversed the phenomenon. Collectively, our in vivo and in vitro findings support that TWIST1 collaborates with the EGF pathway in promoting EMT in EGFR mutated lung adenocarcinoma and that large series of EGFR mutated lung cancer patients are needed to further define the prognostic role of TWIST1 reactivation in this subgroup.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22272264</pmid><doi>10.1371/journal.pone.0029954</doi><tpages>e29954</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2012-01, Vol.7 (1), p.e29954-e29954 |
issn | 1932-6203 1932-6203 |
language | eng |
recordid | cdi_plos_journals_1323077581 |
source | Publicly Available Content (ProQuest); PubMed Central |
subjects | Activation Adenocarcinoma Adenocarcinoma - genetics Adenocarcinoma - metabolism Adenocarcinoma - pathology Aged Aged, 80 and over Antigens, CD - genetics Antigens, CD - metabolism Biology Blotting, Western Cadherins - genetics Cadherins - metabolism Cancer Cell growth Cell Line, Tumor Cell Movement - genetics Chromosome 7 Cooperation Copy number Development and progression E-cadherin Embryogenesis Embryonic growth stage Epidermal growth factor Epidermal Growth Factor - pharmacology Epidermal growth factor receptors Epidermal growth factors Epithelial-Mesenchymal Transition - drug effects Epithelial-Mesenchymal Transition - genetics Female Gene expression Gene Expression Regulation, Neoplastic Genetic aspects Head & neck cancer Health aspects Humans Hypoxia Immunohistochemistry Kaplan-Meier Estimate Kinases Lung cancer Lung diseases Lung Neoplasms - genetics Lung Neoplasms - metabolism Lung Neoplasms - pathology Male Medicine Mesenchyme Metastases Metastasis Middle Aged Mortality Motility Mutation Nuclear Proteins - genetics Nuclear Proteins - metabolism Pathology Patients Receptor, Epidermal Growth Factor - genetics Receptor, Epidermal Growth Factor - metabolism Reverse Transcriptase Polymerase Chain Reaction Ribonucleic acid RNA RNA Interference Senescence Smoking Stem cells Surgery Thoracic surgery Tumor cell lines Tumors Twist-Related Protein 1 - genetics Twist-Related Protein 1 - metabolism |
title | TWIST1 a new determinant of epithelial to mesenchymal transition in EGFR mutated lung adenocarcinoma |
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