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) (PMCID:PMC6591140)
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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: | Anderson, Professor Kurt and Sansom, Professor Owen and Campbell, Dr Andrew |
| 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 > School of Cancer Sciences |
| Journal Name: | Cancer Cell |
| Publisher: | Elsevier |
| ISSN: | 1535-6108 |
| ISSN (Online): | 1878-3686 |
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