The formation of metastasis from a primary tumor is achieved through a metamorphosis of adherent tumor cells to highly migratory and invasive cells. We are particularly interested in the fundamental questions on how these cells with an original epithelial imprinting de-differentiate into metastatic tumor cells with a mesenchymal gene expression profile. During this process, also known as EMT (epithelial to mesenchymal transition), tumorigenic cells undergo a major transcriptional reprogramming that leads to the conversion of benign, adhesive cells to malignant, invasive cells. The massive changes in gene expression during EMT argue for a critical role of master regulators that act on the level of chromatin modifications and direct transcriptional control.

To study the epigenetic control of cellular de-differentiation, we induce EMT in vitro by the addition of TGFb to murine epithelial cells and follow the transcriptional and phenotypic changes over time. By combining RNAi screening approach together with microarray analysis and chromatin-immunoprecipitation, we aim at deciphering the complex networks driving EMT. More specifically, we will use a phenotypic microscopy-based screen of transcription (co)factors as well as a functional migration screen to identify and hierarchically group the factors regulating EMT. We are especially interested in epigenetic modifiers and their contribution to EMT and tumor metastasis. Using this approach, we hope to gain a more global understanding of the processes underlying malignant tumor progression and metastasis.