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First published online June 18, 2008
doi: 10.1242/10.1242/jcs.021667

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E-cadherin controls β-catenin and NF-B transcriptional activity in mesenchymal gene expression

Guiomar Solanas^1,*, Montserrat Porta-de-la-Riva^2,*, Cristina Agustí², David Casagolda¹, Francisco Sánchez-Aguilera², María Jesús Larriba³, Ferran Pons², Sandra Peiró², Maria Escrivà², Alberto Muñoz³, Mireia Duñach^1,, Antonio García de Herreros^2,4, and Josep Baulida^2,

¹ Unitat de Biofísica-CEB, Departament de Bioquímica i Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, E-08193 Bellaterra, Spain
² Programa de Recerca en Càncer, IMIM-Hospital del Mar, E-8003, Barcelona, Spain
³ Instituto de Investigaciones Biomédicas `Alberto Sols', Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain
⁴ Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain

Authors for correspondence (e-mails: mireia.dunach{at}uab.cat; agarcia{at}imim.es; jbaulida{at}imim.es)

Accepted 9 April 2008

E-cadherin and its transcriptional repressor Snail1 (Snai1) are two factors that control epithelial phenotype. Expression of Snail1 promotes the conversion of epithelial cells to mesenchymal cells, and occurs concomitantly with the downregulation of E-cadherin and the upregulation of expression of mesenchymal genes such as those encoding fibronectin and LEF1. We studied the molecular mechanism controlling the expression of these genes in mesenchymal cells. Forced expression of E-cadherin strongly downregulated fibronectin and LEF1 RNA levels, indicating that E-cadherin-sensitive factors are involved in the transcription of these genes. E-cadherin overexpression decreased the transcriptional activity of the fibronectin promoter and reduced the interaction of β-catenin and NF-B with this promoter. Similar to β-catenin, NF-B was found, by co-immunoprecipitation and pull-down assays, to be associated with E-cadherin and other cell-adhesion components. Interaction of the NF-B p65 subunit with E-cadherin or β-catenin was reduced when adherens junctions were disrupted by K-ras overexpression or by E-cadherin depletion using siRNA. These conditions did not affect the association of p65 with the NF-B inhibitor IB. The functional significance of these results was stressed by the stimulation of NF-B transcriptional activity, both basal and TNF--stimulated, induced by an E-cadherin siRNA. Therefore, these results demonstrate that E-cadherin not only controls the transcriptional activity of β-catenin but also that of NF-B. They indicate too that binding of this latter factor to the adherens junctional complex prevents the transcription of mesenchymal genes.

Key words: Cadherin, EMT, NF-B, Snail, β-catenin

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