Silvia von Karstedt, Annalisa Conti, Max Nobis, Antonella Montinaro, Torsten Hartwig, Johannes Lemke, Karen Legler, Franka Annewanter, Andrew D Campbell, Lucia Taraborrelli, Anne Grosse-Wilde, Johannes F Coy, Mona A El-Bahrawy, Frank Bergmann, Ronald Koschny, Jens Werner, Tom M Ganten, Thomas Schweiger, Konrad Hoetzenecker, Istvan Kenessey, Balazs Hegedüs, Michael Bergmann, Charlotte Hauser, Jan-Hendrik Egberts, Thomas Becker, Christoph Röcken, Holger Kalthoff, Anna Trauzold, Kurt I Anderson, Owen J Sansom, Henning Walczak
Many cancers harbor oncogenic mutations of KRAS. Effectors mediating cancer progression, invasion, and metastasis in KRAS-mutated cancers are only incompletely understood. Here we identify cancer cell-expressed murine TRAIL-R, whose main function ascribed so far has been the induction of apoptosis as a crucial mediator of KRAS-driven cancer progression, invasion, and metastasis and in vivo Rac-1 activation. Cancer cell-restricted genetic ablation of murine TRAIL-R in autochthonous KRAS-driven models of non-small-cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC) reduces tumor growth, blunts metastasis, and prolongs survival by inhibiting cancer cell-autonomous migration, proliferation, and invasion...
April 13, 2015: Cancer Cell