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Targeting of Fn14 Prevents Cancer-Induced Cachexia and Prolongs Survival.
Johnston, Amelia J; Murphy, Kate T; Jenkinson, Laura; Laine, David; Emmrich, Kerstin; Faou, Pierre; Weston, Ross; Jayatilleke, Krishnath M; Schloegel, Jessie; Talbo, Gert; Casey, Joanne L; Levina, Vita; Wong, W Wei-Lynn; Dillon, Helen; Sahay, Tushar; Hoogenraad, Joan; Anderton, Holly; Hall, Cathrine; Schneider, Pascal; Tanzer, Maria; Foley, Michael; Scott, Andrew M; Gregorevic, Paul; Liu, Spring Yingchun; Burkly, Linda C; Lynch, Gordon S; Silke, John; Hoogenraad, Nicholas J.
Affiliation
  • Johnston AJ; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia. Electronic address: a.johnston@latrobe.edu.au.
  • Murphy KT; Basic and Clinical Myology Laboratory, Department of Physiology, The University of Melbourne, Melbourne, VIC 3010, Australia.
  • Jenkinson L; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia.
  • Laine D; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia.
  • Emmrich K; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia.
  • Faou P; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia.
  • Weston R; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia.
  • Jayatilleke KM; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia.
  • Schloegel J; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia.
  • Talbo G; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia.
  • Casey JL; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia.
  • Levina V; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia.
  • Wong WW; Institute of Experimental Immunology, University of Zürich, Zürich 8057, Switzerland.
  • Dillon H; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia.
  • Sahay T; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia.
  • Hoogenraad J; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia.
  • Anderton H; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia; The Walter and Eliza Hall Institute, Melbourne, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, VIC 3050, Australia.
  • Hall C; The Walter and Eliza Hall Institute, Melbourne, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, VIC 3050, Australia.
  • Schneider P; Department of Biochemistry, University of Lausanne, Epalinges 1066, Switzerland.
  • Tanzer M; The Walter and Eliza Hall Institute, Melbourne, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, VIC 3050, Australia.
  • Foley M; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia.
  • Scott AM; Olivia Newton-John Cancer Research Institute, Melbourne, VIC 3084, Australia; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia.
  • Gregorevic P; Baker IDI Heart and Diabetes Institute, Melbourne, VIC 3004, Australia; Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
  • Liu SY; Broad Institute, MIT and Harvard, Cambridge, MA 02142, USA.
  • Burkly LC; Department of Immunology, Biogen Idec, 14 Cambridge Center, Cambridge, MA 02142, USA.
  • Lynch GS; Basic and Clinical Myology Laboratory, Department of Physiology, The University of Melbourne, Melbourne, VIC 3010, Australia.
  • Silke J; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia; The Walter and Eliza Hall Institute, Melbourne, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, VIC 3050, Australia.
  • Hoogenraad NJ; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia. Electronic address: n.hoogenraad@latrobe.edu.au.
Cell ; 162(6): 1365-78, 2015 Sep 10.
Article in En | MEDLINE | ID: mdl-26359988
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cachexia / Receptors, Tumor Necrosis Factor / Neoplasms Limits: Animals / Female / Humans Language: En Journal: Cell Year: 2015 Type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cachexia / Receptors, Tumor Necrosis Factor / Neoplasms Limits: Animals / Female / Humans Language: En Journal: Cell Year: 2015 Type: Article