Targeting CD44v6, a co-receptor for Met and VEGFR-2 in endothelial cells, inhibits tumour angiogenesis [Elektronische Ressource] / vorgelegt von Martina Tremmel

Targeting CD44v6, a co-receptor for Met and VEGFR-2 in endothelial cells, inhibits tumour angiogenesis INAUGURAL-DISSERTATION zur Erlangung der Doktorwürde der Naturwissenschaftlich-Mathematischen Gesamtfakultät der Ruprecht-Karls-Universität Heidelberg 2009 vorgelegt von Martina Tremmel aus Frankfurt / Main Tag der mündlichen Prüfung: Gutachter: Prof. Dr. Uwe Strähle Dr. Véronique Orian-Rousseau, PD Abstract ABSTRACT Members of the transmembrane glycoprotein family CD44 containing variant exon v6 sequences have been shown to act as co-receptors for the receptor tyrosine kinase (RTK) Met in epithelial cells (Orian-Rousseau et al. 2002; Orian-Rousseau et al. 2007). This work demonstrates that the co-receptor function of CD44v6 can be expanded to endothelial cells (ECs) and to another RTK, VEGFR-2. As VEGFR-2 is the most prominent RTK in angiogenesis, these findings indicate that also CD44v6 is strongly involved in this process. Both in the case of VEGFR-2 and Met, CD44v6 is not only required for receptor activation, a function performed by the CD44v6 ectodomain, but also plays a role in signal transduction. The intracellular domain of CD44v6 recruits ERM (ezrin, radixin, moesin) proteins bound to the actin cytoskeleton, a prerequisite for activation of further components of the signalling cascades.