Vincent, 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, Jonas2019-02-182019-02-182009Vincent 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/ncb19051465-7392http://hdl.handle.net/10230/36611Epithelial-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.application/pdfeng© 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/ncb1905Smad3 -- MetabolismeSmad4 -- MetabolismeFactors de transcripcióFactor de creixement transformant betainfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/ncb1905info:eu-repo/semantics/openAccess