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Snail promotes Wnt target gene expression and interacts with β-catenin

Oncogene volume 27, pages 5075–5080 (2008)Cite this article

Abstract

The transcription factor snail represses epithelial gene expression and thereby promotes epithelial-mesenchymal transitions (EMT) and tumor invasion. The Wnt/β-catenin pathway is also involved in EMT and was shown to activate snail. Here, we demonstrate that snail increases Wnt reporter gene activity induced by β-catenin, LRP6 or dishevelled, and also promotes transcription activated by GAL4-β-catenin fusion proteins. Snail mutants lacking the transcriptional repressor domain also stimulate β-catenin-dependent transcription indicating that downregulation of snail target genes is not required for this activity. Snail interacts with β-catenin in immunoprecipitation experiments at its N-terminus, which is required for activation by snail. In colorectal cancer cell lines, overexpression of snail leads to increased expression of Wnt target genes, whereas downregulation of endogenous snail by siRNA reduces target gene expression. Our data indicate a positive feedback stimulation of the Wnt pathway by activation of snail.

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References

  • Bachelder RE, Yoon SO, Franci C, de Herreros AG, Mercurio AM . (2005). Glycogen synthase kinase-3 is an endogenous inhibitor of Snail transcription: implications for the epithelial-mesenchymal transition. J Cell Biol 168: 29–33.

    Article  CAS  Google Scholar 

  • Barrallo-Gimeno A, Nieto MA . (2005). The Snail genes as inducers of cell movement and survival: implications in development and cancer. Development 132: 3151–3161.

    Article  CAS  Google Scholar 

  • Batlle E, Sancho E, Franci C, Dominguez D, Monfar M, Baulida J et al. (2000). The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol 2: 84–89.

    Article  CAS  Google Scholar 

  • Behrens J . (2005). The role of the Wnt signalling pathway in colorectal tumorigenesis. Biochem Soc Trans 33: 672–675.

    Article  CAS  Google Scholar 

  • Brabletz T, Jung A, Reu S, Porzner M, Hlubek F, Kunz-Schughart LA et al. (2001). Variable beta-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment. Proc Natl Acad Sci USA 98: 10356–10361.

    Article  CAS  Google Scholar 

  • Brembeck FH, Schwarz-Romond T, Bakkers J, Wilhelm S, Hammerschmidt M, Birchmeier W . (2004). Essential role of BCL9-2 in the switch between beta-catenin's adhesive and transcriptional functions. Genes Dev 18: 2225–2230.

    Article  CAS  Google Scholar 

  • Cano A, Perez-Moreno MA, Rodrigo I, Locascio A, Blanco MJ, del Barrio MG et al. (2000). The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol 2: 76–83.

    Article  CAS  Google Scholar 

  • Dale JK, Malapert P, Chal J, Vilhais-Neto G, Maroto M, Johnson T et al. (2006). Oscillations of the snail genes in the presomitic mesoderm coordinate segmental patterning and morphogenesis in vertebrate somitogenesis. Dev Cell 10: 355–366.

    Article  CAS  Google Scholar 

  • De Craene B, Gilbert B, Stove C, Bruyneel E, van Roy F, Berx G . (2005). The transcription factor snail induces tumor cell invasion through modulation of the epithelial cell differentiation program. Cancer Res 65: 6237–6244.

    Article  CAS  Google Scholar 

  • Hsu SC, Galceran J, Grosschedl R . (1998). Modulation of transcriptional regulation by LEF-1 in response to Wnt-1 signaling and association with beta-catenin. Mol Cell Biol 18: 4807–4818.

    Article  CAS  Google Scholar 

  • Huber MA, Kraut N, Beug H . (2005). Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr Opin Cell Biol 17: 548–558.

    Article  CAS  Google Scholar 

  • Jho EH, Zhang T, Domon C, Joo CK, Freund JN, Costantini F . (2002). Wnt/beta-catenin/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway. Mol Cell Biol 22: 1172–1183.

    Article  CAS  Google Scholar 

  • Krieghoff E, Behrens J, Mayr B . (2006). Nucleo-cytoplasmic distribution of beta-catenin is regulated by retention. J Cell Sci 119: 1453–1463.

    Article  CAS  Google Scholar 

  • Lustig B, Jerchow B, Sachs M, Weiler S, Pietsch T, Karsten U et al. (2002). Negative feedback loop of Wnt signaling through upregulation of conductin/axin2 in colorectal and liver tumors. Mol Cell Biol 22: 1184–1193.

    Article  CAS  Google Scholar 

  • Peinado H, Ballestar E, Esteller M, Cano A . (2004). Snail mediates E-cadherin repression by the recruitment of the Sin3A/histone deacetylase 1 (HDAC1)/HDAC2 complex. Mol Cell Biol 24: 306–319.

    Article  CAS  Google Scholar 

  • Roy HK, Iversen P, Hart J, Liu Y, Koetsier JL, Kim Y et al. (2004). Down-regulation of SNAIL suppresses MIN mouse tumorigenesis: modulation of apoptosis, proliferation, and fractal dimension. Mol Cancer Ther 3: 1159–1165.

    Article  CAS  Google Scholar 

  • Yook JI, Li XY, Ota I, Hu C, Kim HS, Kim NH et al. (2006). A Wnt-Axin2-GSK3beta cascade regulates Snail1 activity in breast cancer cells. Nat Cell Biol 8: 1398–1406.

    Article  CAS  Google Scholar 

  • Zhou BP, Deng J, Xia W, Xu J, Li YM, Gunduz M et al. (2004). Dual regulation of Snail by GSK-3beta-mediated phosphorylation in control of epithelial-mesenchymal transition. Nat Cell Biol 6: 931–940.

    Article  CAS  Google Scholar 

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Acknowledgements

We thank F Costantini for providing the Axin2 promoter reporter construct, E Krieghoff for LRP6da and β-catenin constructs and M van de Wetering for TOP and FOPglow constructs.

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Authors and Affiliations

  1. Nikolaus-Fiebiger-Center for Molecular Medicine, University Erlangen-Nürnberg, Erlangen, Germany

    V Stemmer & J Behrens

  2. Department for Molecular Biomedical Research (DMBR), Molecular and Cellular Oncology, VIB-Ghent University, Ghent, Zwijnaarde, Belgium

    B de Craene & G Berx

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  1. V Stemmer
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  2. B de Craene
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  3. G Berx
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  4. J Behrens
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Correspondence to J Behrens.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Stemmer, V., de Craene, B., Berx, G. et al. Snail promotes Wnt target gene expression and interacts with β-catenin. Oncogene 27, 5075–5080 (2008). https://doi.org/10.1038/onc.2008.140

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