TY - JOUR
T1 - Cancer cell-autonomous TRAIL-R signaling promotes KRAS-Driven cancer progression, invasion, and metastasis
AU - von Karstedt, Silvia
AU - Conti, Annalisa
AU - Nobis, Max
AU - Montinaro, Antonella
AU - Hartwig, Torsten
AU - Lemke, Johannes
AU - Legler, Karen
AU - Annewanter, Franka
AU - Campbell, Andrew D.
AU - Taraborrelli, Lucia
AU - Grosse-Wilde, Anne
AU - Coy, Johannes F.
AU - El-Bahrawy, Mona A.
AU - Bergmann, Frank
AU - Koschny, Ronald
AU - Werner, Jens
AU - Ganten, Tom M.
AU - Schweiger, Thomas
AU - Hoetzenecker, Konrad
AU - Kenessey, Istvan
AU - Hegedüs, Balazs
AU - Bergmann, Michael
AU - Hauser, Charlotte
AU - Egberts, Jan Hendrik
AU - Becker, Thomas
AU - Röcken, Christoph
AU - Kalthoff, Holger
AU - Trauzold, Anna
AU - Anderson, Kurt I.
AU - Sansom, Owen J.
AU - Walczak, Henning
PY - 2015/4/13
Y1 - 2015/4/13
N2 - 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 invivo 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.
AB - 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 invivo 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.
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U2 - 10.1016/j.ccell.2015.02.014
DO - 10.1016/j.ccell.2015.02.014
M3 - Article
C2 - 25843002
AN - SCOPUS:84928080746
VL - 27
SP - 561
EP - 573
JO - Cancer Cell
JF - Cancer Cell
SN - 1535-6108
IS - 4
ER -