IMIM - Institut Hospital del Mar d'Investigacions Mèdiques

Epithelial-Mesenchymal Transition and Tumor Progression Antonio García de Herreros

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Characterization of the mechanisms controlling E-cadherin gene expression in tumor cells and their implications in tumor development. Dr. Garcia de Herreros

In 2000 our group reported the characterization of Snail1 transcription factor as a key repressor of E-cadherin expression, a crucial protein for determining epithelial phenotype (Batlle et al., Nat Cell Biol 2000, 2: 84 -89); Snail1 also induces the conversion of epithelial cells to mesenchymal cells (epithelial to mesenchymal transition, EMT). This discovery redirected the group's line of research to the study of this factor and its function as a determinant of EMT, a transition that not only confers the cells increased invasive capacity but also greater resistance to apoptosis and even characteristics of mesenchymal stem cells. In addition to other lines, which are indicated in the projects of Drs Peiró, Baulida i Díaz, Dr García de Herreros' group is interested in the study of the functions of Snail1 in adult animals, with a special emphasis on its role in mesenchymal cells and its relation to neoplasms. Recent results indicate that Snail1 is needed for fibroblast activation and required for a full functional response to a TGF-b.

The three latest publications on this topic are:

  • DAVE, N., GUAITA-ESTERUELAS, S., GUTARRA, S., FRIAS, A., BELTRAN, M., PEIRO, S., GARCIA DE HERREROS, A. Functional cooperation between Snail1 and Twist in the regulation of Zeb1 expression during epithelial-to-mesenchymal transition. J. Biol. Chem., 2011, 286, 12024-12032.
  • VILLAGRASA, P., DIAZ, V.M., VIÑAS-CASTELLS, R., PEIRÓ, S., DEL VALLE-PÉREZ, B., DAVE, N., RODRIGUEZ-ASIAIN, A., CASAL, J. I., LIZCANO, J.M., DUÑACH, M.*, GARCIA DE HERREROS, A.* (*corresponding authors) (2012). Akt2 interacts with Snail1 in E-cadherin promoter. Oncogene.31, 4022-4033.
  • BATLLE, R., ALBA, L., LOUBAT-CASANOVAS, J., STANISAVLJEVIC, J., ARMENTEROS, E., FRANCI, C., MARTIN-CABALLERO, J., BONILLA, F., BAULIDA, J., GRIDLEY, T., GARCIA DE HERREROS A. (2013) Snail1 controls TGF-b responsiveness and differentiation of Mesenchymal Stem Cells. Oncogene 32, 3381-3389.

Figure 2. Effect of Snail1 depletion on the effect of TGF-b on the differentiation of mesenchymal stem cells (MSCs) into osteoblasts. For more details, Batlle et al (2013).

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