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Targeting of Fn14 prevents cancer-induced cachexia and prolongs survival


Johnston, AJ; Murphy, KT; Jenkinson, L; Laine, D; Emmrich, K; Faou, P; Weston, R; Jayatilleke, KM; Schloegel, J; Talbo, G; Casey, JL; Levina, V; Wong, WW; Dillon, H; Sahay, T; Hoogenraad, J; Anderton, H; Hall, C; Schneider, P; Tanzer, M; Foley, M; Scott, AM; Gregorevic, P; Liu, SY; Burkly, LC; Lynch, GS; Silke, J; Hoogenraad, NJ
2015-09-10
Cell
Journal Article
162
6
1365-78
The cytokine TWEAK and its cognate receptor Fn14 are members of the TNF/TNFR superfamily and are upregulated in tumors. We found that Fn14, when expressed in tumors, causes cachexia and that antibodies against Fn14 dramatically extended lifespan by inhibiting tumor-induced weight loss although having only moderate inhibitory effects on tumor growth. Anti-Fn14 antibodies prevented tumor-induced inflammation and loss of fat and muscle mass. Fn14 signaling in the tumor, rather than host, is responsible for inducing this cachexia because tumors in Fn14- and TWEAK-deficient hosts developed cachexia that was comparable to that of wild-type mice. These results extend the role of Fn14 in wound repair and muscle development to involvement in the etiology of cachexia and indicate that Fn14 antibodies may be a promising approach to treat cachexia, thereby extending lifespan and improving quality of life for cancer patients.
Cell Press
Cell Signalling and Cell Death
10.1016/j.cell.2015.08.031
26359988
Refer to article for additional funding acknowledgements
Refer to copyright notice on published article.

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Creation Date 2015-09-24 02:12:25 Last Modified 2016-03-30 03:28:34