| Literature DB >> 25843002 |
Silvia von Karstedt1, Annalisa Conti2, Max Nobis3, Antonella Montinaro1, Torsten Hartwig1, Johannes Lemke1, Karen Legler4, Franka Annewanter4, Andrew D Campbell3, Lucia Taraborrelli1, Anne Grosse-Wilde5, Johannes F Coy6, Mona A El-Bahrawy7, Frank Bergmann8, Ronald Koschny9, Jens Werner10, Tom M Ganten9, Thomas Schweiger11, Konrad Hoetzenecker12, Istvan Kenessey13, Balazs Hegedüs14, Michael Bergmann15, Charlotte Hauser16, Jan-Hendrik Egberts16, Thomas Becker16, Christoph Röcken17, Holger Kalthoff4, Anna Trauzold18, Kurt I Anderson3, Owen J Sansom3, Henning Walczak19.
Abstract
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. Consistent with this, high TRAIL-R2 expression correlates with invasion of human PDAC into lymph vessels and with shortened metastasis-free survival of KRAS-mutated colorectal cancer patients.Entities:
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Year: 2015 PMID： 25843002 PMCID： PMC6591140 DOI： 10.1016/j.ccell.2015.02.014
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743