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In der ersten Netzschau im Neuen Jahr geht es um das (vermeintliche) Aussterben des Folterverbots in den USA, Drohnen in Europa, Demokratisierungstrends in den kommenden zehn Jahren, die Finanzierung des UN-Menschenrechtspfeilers und die Konkurrenz zwischen al Qaida und dem Islamischen Staat – auch im Lichte der Anschläge von Paris.
Second mitochondria-derived activator of caspase (Smac) mimetics are considered as promising anticancer therapeutics that are currently under investigation in early clinical trials. They induce apoptosis by antagonizing inhibitor of apoptosis proteins, which are frequently overexpressed in cancer. We previously reported that Smac mimetics, such as BV6, additionally exert non-apoptotic functions in glioblastoma (GBM) cells by stimulating migration and invasion in a nuclear factor kappa B (NF-κB)-dependent manner. Because NF-κB target genes mediating these effects are largely unknown, we performed whole-genome expression analyses. Here, we identify chemokine (C-C motif) ligand 2 (CCL2) as the top-listed NF-κB-regulated gene being upregulated upon BV6 treatment in GBM cells. BV6-induced upregulation and secretion of CCL2 are required for migration and invasion of GBM cells because knockdown of CCL2 in GBM cells abolishes these effects. Co-culture experiments of GBM cells with non-malignant astroglial cells reveal that BV6-stimulated secretion of CCL2 by GBM cells into the supernatant triggers migration of astroglial cells toward GBM cells because CCL2 knockdown in BV6-treated GBM cells impedes BV6-stimulated migration of astroglial cells. In conclusion, we identify CCL2 as a BV6-induced NF-κB target gene that triggers migration and invasion of GBM cells and exerts paracrine effects on the GBM's microenvironment by stimulating migration of astroglial cells. These findings provide novel insights into the biological functions of Smac mimetics with important implications for the development of Smac mimetics as cancer therapeutics.
Die Goethe-Universität Frankfurt am Main verpflichtet sich der Familienfreundlichkeit als eines der zentralen Querschnittsthemen der Universität. Ziel ist es, in Studium, Forschung, Lehre und Verwaltung nachhaltig bessere Rahmenbedingungen für Hochschulmitglieder mit Familienaufgaben zu schaffen. Familie umfasst dabei über die klassische Kernfamilie hinaus alle Lebensgemeinschaften, in denen eine langfristige soziale Verantwortung für andere wahrgenommen wird. ...