Differentielle Regulation der Transkription während Veränderungen der Krebszell-Motilität

Cancer metastasis accounts for approximately 90% of deaths from solid tumours and represents a major challenge for exploratory research. Recent advances have shown that carcinoma progression often involves epithelial-mesenchymal transition (EMT) and that individual cancer cells invade the surrounding tissue by either a mesenchymal or an amoeboid mode of migration. Amongst many other factors, the transcriptional coactivators of the MAL/MRTF family are required for both EMT induction and for migration, invasion and metastasis in vitro and in vivo. However, whether MAL influences the mode of motility in 3 D is unknown. We have recently demonstrated that MAL is activated during disassembly of epithelial junctions and EMT through activation of Rac and dissociation of MAL from G actin. In addition to this regulation by signalling, our own preliminary experiments showed an induction of MAL/MRTF-A protein and mRNA levels in several EMT models. In this project we analyse the mechanisms of MAL induction during EMT and its effect on mesenchymal and amoeboid cell motility.