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.
Genregulation, Molekulare Medizin, Signaltransduktion, Zellbiologie
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