Targeting of Fn14 prevents cancer-induced cachexia and prolongs survival
- Author(s)
- 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;
- Details
- Publication Year 2015-09-10,Volume 162,Issue #6,Page 1365-78
- Journal Title
- Cell
- Publication Type
- Journal Article
- Abstract
- 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.
- Publisher
- Cell Press
- Research Division(s)
- Cell Signalling And Cell Death
- PubMed ID
- 26359988
- Publisher's Version
- https://doi.org/10.1016/j.cell.2015.08.031
- NHMRC Grants
- NHMRC/541901, NHMRC/1058190, NHMRC/1075504,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2015-09-24 02:12:25
Last Modified: 2016-03-30 03:28:34