Transforming growth factor beta-1 induces snail transcription factor in epithelial cell lines: mechanisms for epithelial mesenchymal transitions.

The Snail transcription factor has been described recently as a strong repressor of E-cadherin in epithelial cell lines, where its stable expression leads to the loss of E-cadherin expression and induces epithelial-mesenchymal transitions and an invasive phenotype. The mechanisms regulating Snail ex...

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Detalles Bibliográficos
Autores: Peinado, Hector, Quintanilla, Miguel, Cano, Amparo
Tipo de recurso: artículo
Fecha de publicación:2003
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/17963
Acceso en línea:http://hdl.handle.net/20.500.12105/17963
Access Level:acceso abierto
Palabra clave:Animals
Cadherins
Cell Line
Cell Movement
DNA-Binding Proteins
Dogs
Epithelial Cells
Fibroblast Growth Factor 2
Gene Expression
Genes, ras
Kidney
MAP Kinase Kinase 1
MAP Kinase Kinase 2
MAP Kinase Signaling System
Mesoderm
Mitogen-Activated Protein Kinase Kinases
Phenotype
Phosphatidylinositol 3-Kinases
Promoter Regions, Genetic
Protein Serine-Threonine Kinases
Protein-Tyrosine Kinases
Snail Family Transcription Factors
Transcription Factors
Transforming Growth Factor beta
Transforming Growth Factor beta1
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oai_identifier_str oai:repisalud.isciii.es:20.500.12105/17963
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spelling Transforming growth factor beta-1 induces snail transcription factor in epithelial cell lines: mechanisms for epithelial mesenchymal transitions.Peinado, HectorQuintanilla, MiguelCano, AmparoAnimalsCadherinsCell LineCell MovementDNA-Binding ProteinsDogsEpithelial CellsFibroblast Growth Factor 2Gene ExpressionGenes, rasKidneyMAP Kinase Kinase 1MAP Kinase Kinase 2MAP Kinase Signaling SystemMesodermMitogen-Activated Protein Kinase KinasesPhenotypePhosphatidylinositol 3-KinasesPromoter Regions, GeneticProtein Serine-Threonine KinasesProtein-Tyrosine KinasesSnail Family Transcription FactorsTranscription FactorsTransforming Growth Factor betaTransforming Growth Factor beta1The Snail transcription factor has been described recently as a strong repressor of E-cadherin in epithelial cell lines, where its stable expression leads to the loss of E-cadherin expression and induces epithelial-mesenchymal transitions and an invasive phenotype. The mechanisms regulating Snail expression in development and tumor progression are not yet known. We show here that transforming growth factor beta-1 (TGFbeta1) induces Snail expression in Madin-Darby canine kidney cells and triggers epithelial-mesenchymal transitions by a mechanism dependent on the MAPK signaling pathway. Furthermore, TGFbeta1 induces the activity of Snail promoter, whereas fibroblast growth factor-2 has a milder effect but cooperates with TGFbeta1 in the induction of Snail promoter. Interestingly, TGFbeta1-mediated induction of Snail promoter is blocked by a dominant negative form of H-Ras (N17Ras), whereas oncogenic H-Ras (V12Ras) induces Snail promoter activity and synergistically cooperates with TGFbeta1. The effects of TGFbeta1 on Snail promoter are dependent of MEK1/2 activity but are apparently independent of Smad4 activity. In addition, H-Ras-mediated induction of Snail promoter, alone or in the presence of TGFbeta1, depends on both MAPK and phosphatidylinositol 3-kinase activities. These data support that MAPK and phosphatidylinositol 3-kinase signaling pathways are implicated in TGFbeta1-mediated induction of Snail promoter, probably through Ras activation and its downstream effectors.Elsevier20242024-02-1220032003-06-0620032003-06-06journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/17963reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/179632026-06-12T12:43:37Z
dc.title.none.fl_str_mv Transforming growth factor beta-1 induces snail transcription factor in epithelial cell lines: mechanisms for epithelial mesenchymal transitions.
title Transforming growth factor beta-1 induces snail transcription factor in epithelial cell lines: mechanisms for epithelial mesenchymal transitions.
spellingShingle Transforming growth factor beta-1 induces snail transcription factor in epithelial cell lines: mechanisms for epithelial mesenchymal transitions.
Peinado, Hector
Animals
Cadherins
Cell Line
Cell Movement
DNA-Binding Proteins
Dogs
Epithelial Cells
Fibroblast Growth Factor 2
Gene Expression
Genes, ras
Kidney
MAP Kinase Kinase 1
MAP Kinase Kinase 2
MAP Kinase Signaling System
Mesoderm
Mitogen-Activated Protein Kinase Kinases
Phenotype
Phosphatidylinositol 3-Kinases
Promoter Regions, Genetic
Protein Serine-Threonine Kinases
Protein-Tyrosine Kinases
Snail Family Transcription Factors
Transcription Factors
Transforming Growth Factor beta
Transforming Growth Factor beta1
title_short Transforming growth factor beta-1 induces snail transcription factor in epithelial cell lines: mechanisms for epithelial mesenchymal transitions.
title_full Transforming growth factor beta-1 induces snail transcription factor in epithelial cell lines: mechanisms for epithelial mesenchymal transitions.
title_fullStr Transforming growth factor beta-1 induces snail transcription factor in epithelial cell lines: mechanisms for epithelial mesenchymal transitions.
title_full_unstemmed Transforming growth factor beta-1 induces snail transcription factor in epithelial cell lines: mechanisms for epithelial mesenchymal transitions.
title_sort Transforming growth factor beta-1 induces snail transcription factor in epithelial cell lines: mechanisms for epithelial mesenchymal transitions.
dc.creator.none.fl_str_mv Peinado, Hector
Quintanilla, Miguel
Cano, Amparo
author Peinado, Hector
author_facet Peinado, Hector
Quintanilla, Miguel
Cano, Amparo
author_role author
author2 Quintanilla, Miguel
Cano, Amparo
author2_role author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv Animals
Cadherins
Cell Line
Cell Movement
DNA-Binding Proteins
Dogs
Epithelial Cells
Fibroblast Growth Factor 2
Gene Expression
Genes, ras
Kidney
MAP Kinase Kinase 1
MAP Kinase Kinase 2
MAP Kinase Signaling System
Mesoderm
Mitogen-Activated Protein Kinase Kinases
Phenotype
Phosphatidylinositol 3-Kinases
Promoter Regions, Genetic
Protein Serine-Threonine Kinases
Protein-Tyrosine Kinases
Snail Family Transcription Factors
Transcription Factors
Transforming Growth Factor beta
Transforming Growth Factor beta1
topic Animals
Cadherins
Cell Line
Cell Movement
DNA-Binding Proteins
Dogs
Epithelial Cells
Fibroblast Growth Factor 2
Gene Expression
Genes, ras
Kidney
MAP Kinase Kinase 1
MAP Kinase Kinase 2
MAP Kinase Signaling System
Mesoderm
Mitogen-Activated Protein Kinase Kinases
Phenotype
Phosphatidylinositol 3-Kinases
Promoter Regions, Genetic
Protein Serine-Threonine Kinases
Protein-Tyrosine Kinases
Snail Family Transcription Factors
Transcription Factors
Transforming Growth Factor beta
Transforming Growth Factor beta1
description The Snail transcription factor has been described recently as a strong repressor of E-cadherin in epithelial cell lines, where its stable expression leads to the loss of E-cadherin expression and induces epithelial-mesenchymal transitions and an invasive phenotype. The mechanisms regulating Snail expression in development and tumor progression are not yet known. We show here that transforming growth factor beta-1 (TGFbeta1) induces Snail expression in Madin-Darby canine kidney cells and triggers epithelial-mesenchymal transitions by a mechanism dependent on the MAPK signaling pathway. Furthermore, TGFbeta1 induces the activity of Snail promoter, whereas fibroblast growth factor-2 has a milder effect but cooperates with TGFbeta1 in the induction of Snail promoter. Interestingly, TGFbeta1-mediated induction of Snail promoter is blocked by a dominant negative form of H-Ras (N17Ras), whereas oncogenic H-Ras (V12Ras) induces Snail promoter activity and synergistically cooperates with TGFbeta1. The effects of TGFbeta1 on Snail promoter are dependent of MEK1/2 activity but are apparently independent of Smad4 activity. In addition, H-Ras-mediated induction of Snail promoter, alone or in the presence of TGFbeta1, depends on both MAPK and phosphatidylinositol 3-kinase activities. These data support that MAPK and phosphatidylinositol 3-kinase signaling pathways are implicated in TGFbeta1-mediated induction of Snail promoter, probably through Ras activation and its downstream effectors.
publishDate 2003
dc.date.none.fl_str_mv 2003
2003-06-06
2003
2003-06-06
2024
2024-02-12
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/17963
url http://hdl.handle.net/20.500.12105/17963
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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