The progression of cancer towards malignancy is initiated by tumor cells that locally
invade the surrounding tissue, allowing them to reach the blood stream and form
distant metastases. One of the processes contributing to this malignant behavior is
termed Epithelial Mesenchymal Transition (EMT), whereby cells loose the capacity to
adhere to one another and acquire motile capacities. Additionally, EMT goes hand in
hand with resistance to cell death induced by chemotherapeutic agents, as such
impairing successful anti-cancer treatment. The aim of this project is to identify novel
genes which are necessary for the induction and maintenance of EMT and which are
also involved in mechanisms that lead to resistance of cell death. For this purpose,
we will conduct an siRNA screening targeting the druggable genome in EMT related
cellular cancer models. The screening readout will be based on typical epithelial and
mesenchymal marker genes. The discovered hits will be further examined for their
involvement in resistance to cell death by means of automated high content
microscopy. The selected positive hits will subsequently be analyzed in alternative in
vitro and in vivo cancer models. The ultimate goal of this project is to identify
druggable modulators of EMT which are also contributing towards resistance to cell
death. Targeting these factors would result in impairment of the malignant behavior of
cancer cells and sensitizes these cells for chemotherapeutical mediated cell death.