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Cancer Cell-Autonomous TRAIL-R Signaling Promotes KRAS-driven Cancer Progression, Invasion, and Metastasis

Cancer Cell-Autonomous TRAIL-R Signaling Promotes KRAS-driven Cancer Progression, Invasion, and Metastasis

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, etc.

Cancer Cell. 2015 Apr 13;27(4):561-73.

PMID: 25843002

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42412946	TRAIL murine			Price

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