A SNAIL1-SMAD3/4 transcriptional repressor complex promotes TGF-beta mediated epithelial-mesenchymal transition

Epithelial-mesenchymal transition (EMT) is essential for organogenesis and is triggered during carcinoma progression to an invasive state. Transforming growth factor-beta (TGF-beta) cooperates with signalling pathways, such as Ras and Wnt, to induce EMT, but the molecular mechanisms are not clear. H...

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Detalhes bibliográficos
Autores: Vincent, Theresa, Neve, Etienne P.A., Johnson, Jill R., Kukalev, Alexander, Rojo, Federico, Albanell Mestres, Joan, Pietras, Kristian, Virtanen, Ismo, Philipson, Lennart, Leopold, Philip L., Crystal, Ronald G., García de Herreros, Antonio, Moustakas, Aristidis, Petterson, Ralf F., Fuxe, Jonas
Formato: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2009
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/36611
Acesso em linha:http://hdl.handle.net/10230/36611
http://dx.doi.org/10.1038/ncb1905
Access Level:acceso abierto
Palavra-chave:Smad3 -- Metabolisme
Smad4 -- Metabolisme
Factors de transcripció
Factor de creixement transformant beta
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spelling A SNAIL1-SMAD3/4 transcriptional repressor complex promotes TGF-beta mediated epithelial-mesenchymal transitionVincent, TheresaNeve, Etienne P.A.Johnson, Jill R.Kukalev, AlexanderRojo, FedericoAlbanell Mestres, JoanPietras, KristianVirtanen, IsmoPhilipson, LennartLeopold, Philip L.Crystal, Ronald G.García de Herreros, AntonioMoustakas, AristidisPetterson, Ralf F.Fuxe, JonasSmad3 -- MetabolismeSmad4 -- MetabolismeFactors de transcripcióFactor de creixement transformant betaEpithelial-mesenchymal transition (EMT) is essential for organogenesis and is triggered during carcinoma progression to an invasive state. Transforming growth factor-beta (TGF-beta) cooperates with signalling pathways, such as Ras and Wnt, to induce EMT, but the molecular mechanisms are not clear. Here, we report that SMAD3 and SMAD4 interact and form a complex with SNAIL1, a transcriptional repressor and promoter of EMT. The SNAIL1-SMAD3/4 complex was targeted to the gene promoters of CAR, a tight-junction protein, and E-cadherin during TGF-beta-driven EMT in breast epithelial cells. SNAIL1 and SMAD3/4 acted as co-repressors of CAR, occludin, claudin-3 and E-cadherin promoters in transfected cells. Conversely, co-silencing of SNAIL1 and SMAD4 by siRNA inhibited repression of CAR and occludin during EMT. Moreover, loss of CAR and E-cadherin correlated with nuclear co-expression of SNAIL1 and SMAD3/4 in a mouse model of breast carcinoma and at the invasive fronts of human breast cancer. We propose that activation of a SNAIL1-SMAD3/4 transcriptional complex represents a mechanism of gene repression during EMT.Jonas Fuxe was supported by grants from the Swedish Research Council, the Swedish Wenner-Gren Foundation, the Swedish Childhood Cancer Foundation and an International Union Against Cancer (UICC), American Cancer Society International Fellowship for Beginning Investigators. Theresa Vincent was supported by the Swedish Research Council. Philip Leopold and Ronald Crystal were supported by the National Institutes of Health (NIH) by PO1 HL59312 and Antonio García de Herreros, Joan Albanell and Federico Rojo by RD06/0020/109, RD06/0020/040, FIS PI061513, SAF2006-00339 and Fundació Privada CellexNature Research201920192009info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/36611http://dx.doi.org/10.1038/ncb1905reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésNature Cell Biology. 2009 Aug;11(8):943-50© Springer Nature Publishing AG. Vincent T, Neve EP, Johnson JR, Kukalev A, Rojo F, Albanell J et al. A SNAIL1-SMAD3/4 transcriptional repressor complex promotes TGF-beta mediated epithelial-mesenchymal transition. Nat Cell Biol. 2009 Aug; 11(8): 943-50. http://dx.doi.org/10.1038/ncb1905info:eu-repo/semantics/openAccessoai:recercat.cat:10230/366112026-05-29T05:05:01Z
dc.title.none.fl_str_mv A SNAIL1-SMAD3/4 transcriptional repressor complex promotes TGF-beta mediated epithelial-mesenchymal transition
title A SNAIL1-SMAD3/4 transcriptional repressor complex promotes TGF-beta mediated epithelial-mesenchymal transition
spellingShingle A SNAIL1-SMAD3/4 transcriptional repressor complex promotes TGF-beta mediated epithelial-mesenchymal transition
Vincent, Theresa
Smad3 -- Metabolisme
Smad4 -- Metabolisme
Factors de transcripció
Factor de creixement transformant beta
title_short A SNAIL1-SMAD3/4 transcriptional repressor complex promotes TGF-beta mediated epithelial-mesenchymal transition
title_full A SNAIL1-SMAD3/4 transcriptional repressor complex promotes TGF-beta mediated epithelial-mesenchymal transition
title_fullStr A SNAIL1-SMAD3/4 transcriptional repressor complex promotes TGF-beta mediated epithelial-mesenchymal transition
title_full_unstemmed A SNAIL1-SMAD3/4 transcriptional repressor complex promotes TGF-beta mediated epithelial-mesenchymal transition
title_sort A SNAIL1-SMAD3/4 transcriptional repressor complex promotes TGF-beta mediated epithelial-mesenchymal transition
dc.creator.none.fl_str_mv Vincent, Theresa
Neve, Etienne P.A.
Johnson, Jill R.
Kukalev, Alexander
Rojo, Federico
Albanell Mestres, Joan
Pietras, Kristian
Virtanen, Ismo
Philipson, Lennart
Leopold, Philip L.
Crystal, Ronald G.
García de Herreros, Antonio
Moustakas, Aristidis
Petterson, Ralf F.
Fuxe, Jonas
author Vincent, Theresa
author_facet Vincent, Theresa
Neve, Etienne P.A.
Johnson, Jill R.
Kukalev, Alexander
Rojo, Federico
Albanell Mestres, Joan
Pietras, Kristian
Virtanen, Ismo
Philipson, Lennart
Leopold, Philip L.
Crystal, Ronald G.
García de Herreros, Antonio
Moustakas, Aristidis
Petterson, Ralf F.
Fuxe, Jonas
author_role author
author2 Neve, Etienne P.A.
Johnson, Jill R.
Kukalev, Alexander
Rojo, Federico
Albanell Mestres, Joan
Pietras, Kristian
Virtanen, Ismo
Philipson, Lennart
Leopold, Philip L.
Crystal, Ronald G.
García de Herreros, Antonio
Moustakas, Aristidis
Petterson, Ralf F.
Fuxe, Jonas
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Smad3 -- Metabolisme
Smad4 -- Metabolisme
Factors de transcripció
Factor de creixement transformant beta
topic Smad3 -- Metabolisme
Smad4 -- Metabolisme
Factors de transcripció
Factor de creixement transformant beta
description Epithelial-mesenchymal transition (EMT) is essential for organogenesis and is triggered during carcinoma progression to an invasive state. Transforming growth factor-beta (TGF-beta) cooperates with signalling pathways, such as Ras and Wnt, to induce EMT, but the molecular mechanisms are not clear. Here, we report that SMAD3 and SMAD4 interact and form a complex with SNAIL1, a transcriptional repressor and promoter of EMT. The SNAIL1-SMAD3/4 complex was targeted to the gene promoters of CAR, a tight-junction protein, and E-cadherin during TGF-beta-driven EMT in breast epithelial cells. SNAIL1 and SMAD3/4 acted as co-repressors of CAR, occludin, claudin-3 and E-cadherin promoters in transfected cells. Conversely, co-silencing of SNAIL1 and SMAD4 by siRNA inhibited repression of CAR and occludin during EMT. Moreover, loss of CAR and E-cadherin correlated with nuclear co-expression of SNAIL1 and SMAD3/4 in a mouse model of breast carcinoma and at the invasive fronts of human breast cancer. We propose that activation of a SNAIL1-SMAD3/4 transcriptional complex represents a mechanism of gene repression during EMT.
publishDate 2009
dc.date.none.fl_str_mv 2009
2019
2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/36611
http://dx.doi.org/10.1038/ncb1905
url http://hdl.handle.net/10230/36611
http://dx.doi.org/10.1038/ncb1905
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Nature Cell Biology. 2009 Aug;11(8):943-50
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Research
publisher.none.fl_str_mv Nature Research
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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