IMIM - Institut Hospital del Mar d'Investigacions Mèdiques

Epithelial-Mesenchymal Transition and Tumor Progression Antonio García de Herreros

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Analysis of gene expression control by E-cadherin and associated proteins: role in Wnt factor-activated signal transduction pathway. Dr. Garcia de Herreros

The project is carried out in close collaboration with Dr. Mireia Duñach (Universitat Autònoma de Barcelona). Our group has focused to the study of E-caderin-associated proteins, such as β-catenin and p120-catenin, and their dual role as regulators of transcription and modulators of E-cadherin function. In recent years, our work has focussed on p120-catenin which, in addition to binding with and stabilise E-cadherin, has other functions as it controls the activity of the Rho family of GTPases and the Kaiso transcription factor. Our results have indicated that p120-catenin plays an additional role in the Wnt signaling, a pathway that induces β-catenin transcriptional activity. p120-catenin/E-cadherin complex is bound to the LRP5/6 Wnt co-receptor and is necessary for the very early responses to Wnt, such as the activation of CK1e. Furthermore, the separation of the p120-catenin from the complex, which takes place later, is required for the full stabilisation of β-catenin and also p120-catenin to facilitate the transit of β-catenin to the nucleus and eliminate the inhibition caused by Kaiso on the transcriptional activity of the β-catenin/TCF-4 complex. A current model of our vision of this pathway is found in Figure 1.

The three latest publications on this topic are:

  • DEL VALLE-PÉREZ, B., ARQUÉS, O., VINYOLES, M., GARCÍA DE HERREROS, A.*, DUÑACH, M.* (*corresponding authors) (2011). A coordinated action of CK1 isoforms in Wnt signaling. Mol Cel Biol. 31, 2877-2888.
  • VALLS., G., CODINA, M., MILLER, R., DEL VALLE-PÉREZ, B., VINYOLES, M., CAELLES, C., McCREA, P., GARCÍA DE HERREROS, A.*, DUÑACH, M.* (*corresponding authors) (2012). Rac1 activation upon Wnt stimulation requires Rac1 and Vav2 binding to p120-catenin. J. Cell Sci. 125, 5288-5301.
  • VINYOLES, M., DEL VALLE-PÉREZ, B., CURTO, J., VIÑAS-CASTELLS, R., ALBA-CASTELLÓN, L., GARCÍA DE HERREROS, A. *, DUÑACH, M. * (*corresponding authors). (2014) Multivesicular GSK3 sequestration upon Wnt signaling is controlled by p120-catenin/cadherin interaction with LRP5/6. Mol Cell, 53, 444-457.

Figure 1: Fast and late regulation of the activity of GSK3 on β-catenin and the stability of this protein. For more information, Vinyoles et al (2014).

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