The epithelial-to-mesenchymal transition (EMT) plays crucial roles during development, and when activated inappropriately can promote tumour progression and metastasis. To further understand the molecular mechanisms underlying EMT, we have been studying the EMT that underpins the formation of endodermal tissues in Drosophila. Through these studies, we have identified a novel role for GATA transcription factors in inducing a particular kind of EMT. We have found that EMT in the Drosophila endoderm is dependent on the GATA-factor Serpent (Srp), and that Srp acts a potent trigger for EMT when activated ectopically. We have shown that Srp affects EMT through a downregulation of junctional dE-Cad protein, without a block in its transcription. Moreover, this relocalisation of dE-Cad is achieved through the direct repression of Crumbs (Crb) by Srp. Finally, we have found that hGATA-6, an ortholog of Srp, induces EMT in mammalian cells. Similar to Srp, hGATA-6 acts through the downregulation of junctional E-Cad, without blocking its transcription. These results identify set of GATA factors that act as conserved alternative triggers to confer mesenchymal properties on epithelial cells in both development and pathogenesis. Currently we are identifying the downstream targets of GATA factors, and investigating their role in orchestrating EMT.

Trabajo presentado en el 5th International Epithelial-Mesenchymal Transition Meeting, celebrado en Singapur, del 10 al 13 de octubre de 2011

Peer Reviewed