A SNAIL1-SMAD3/4 transcriptional repressor complex promotes TGF-beta mediated epithelial-mesenchymal transition
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- dc.contributor.author Vincent, Theresa
- dc.contributor.author Neve, Etienne P.A.
- dc.contributor.author Johnson, Jill R.
- dc.contributor.author Kukalev, Alexander
- dc.contributor.author Rojo, Federico
- dc.contributor.author Albanell Mestres, Joan
- dc.contributor.author Pietras, Kristian
- dc.contributor.author Virtanen, Ismo
- dc.contributor.author Philipson, Lennart
- dc.contributor.author Leopold, Philip L.
- dc.contributor.author Crystal, Ronald G.
- dc.contributor.author García de Herreros, Antonio
- dc.contributor.author Moustakas, Aristidis
- dc.contributor.author Petterson, Ralf F.
- dc.contributor.author Fuxe, Jonas
- dc.date.accessioned 2019-02-18T12:00:43Z
- dc.date.available 2019-02-18T12:00:43Z
- dc.date.issued 2009
- dc.description.abstract 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.
- dc.description.sponsorship 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 Cellex
- dc.format.mimetype application/pdf
- dc.identifier.citation 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. DOI: 10.1038/ncb1905
- dc.identifier.doi http://dx.doi.org/10.1038/ncb1905
- dc.identifier.issn 1465-7392
- dc.identifier.uri http://hdl.handle.net/10230/36611
- dc.language.iso eng
- dc.publisher Nature Research
- dc.relation.ispartof Nature Cell Biology. 2009 Aug;11(8):943-50
- dc.rights © 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/ncb1905
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.subject.other Smad3 -- Metabolisme
- dc.subject.other Smad4 -- Metabolisme
- dc.subject.other Factors de transcripció
- dc.subject.other Factor de creixement transformant beta
- dc.title A SNAIL1-SMAD3/4 transcriptional repressor complex promotes TGF-beta mediated epithelial-mesenchymal transition
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/acceptedVersion