Cancer cell-autonomous trail-r signaling promotes kras-driven cancer progression, invasion, and metastasis

von Karstedt, S. et al. (2015) Cancer cell-autonomous trail-r signaling promotes kras-driven cancer progression, invasion, and metastasis. Cancer Cell, 27(4), pp. 561-573. (doi:10.1016/j.ccell.2015.02.014) (PMID:25843002)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Campbell, Mr Andrew and Anderson, Professor Kurt and Sansom, Professor Owen
Authors: von Karstedt, S., Conti, A., Nobis, M., Montinaro, A., Hartwig, T., Lemke, J., Legler, K., Annewanter, F., Campbell, A. D., Taraborrelli, L., Grosse-Wilde, A., Coy, J. F., El-Bahrawy, M. A., Bergmann, F., Koschny, R., Werner, J., Ganten, T. M., Schweiger, T., Hoetzenecker, K., Kenessey, I., Hegedüs, B., Bergmann, M., Hauser, C., Egberts, J.-H., Becker, T., Röcken, C., Kalthoff, H., Trauzold, A., Anderson, K. I., Sansom, O. J., and Walczak, H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Cancer Cell
Publisher:Elsevier
ISSN:1535-6108
ISSN (Online):1878-3686

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