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...
| Autores: | , , |
|---|---|
| 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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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 |
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|
| repository.mail.fl_str_mv |
|
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1869417248044613632 |
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15,811543 |