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Ataxin-10 is part of a cachexokine cocktail triggering cardiac metabolic dysfunction in cancer cachexia

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Item Type:Article
Title:Ataxin-10 is part of a cachexokine cocktail triggering cardiac metabolic dysfunction in cancer cachexia
Creators Name:Schaefer, M. and Oeing, C.U. and Rohm, M. and Baysal-Temel, E. and Lehmann, L.H. and Bauer, R. and Volz, H.C. and Boutros, M. and Sohn, D. and Sticht, C. and Gretz, N. and Eichelbaum, K. and Werner, T. and Hirt, M.N. and Eschenhagen, T. and Mueller-Decker, K. and Strobel, O. and Hackert, T. and Krijgsveld, J. and Katus, H.A. and Berriel Diaz, M. and Backs, J. and Herzig, S.
Abstract:Objectives: Cancer cachexia affects the majority of tumor patients and significantly contributes to high mortality rates in these subjects. Despite its clinical importance, the identity of tumor-borne signals and their impact on specific peripheral organ systems, particularly the heart, remain mostly unknown. Methods and results: By combining differential colon cancer cell secretome profiling with large-scale cardiomyocyte phenotyping, we identified a signature panel of seven "cachexokines", including Bridging integrator 1, Syntaxin 7, Multiple inositol-polyphosphate phosphatase 1, Glucosidase alpha acid, Chemokine ligand 2, Adamts like 4, and Ataxin-10, which were both sufficient and necessary to trigger cardiac atrophy and aberrant fatty acid metabolism in cardiomyocytes. As a prototypical example, engineered secretion of Ataxin-10 from non-cachexia-inducing cells was sufficient to induce cachexia phenotypes in cardiomyocytes, correlating with elevated Ataxin-10 serum levels in murine and human cancer cachexia models. Conclusions: As Ataxin-10 serum levels were also found to be elevated in human cachectic cancer patients, the identification of Ataxin-10 as part of a cachexokine cocktail now provides a rational approach towards personalized predictive, diagnostic and therapeutic measures in cancer cachexia.
Keywords:Cancer Cachexia, Ataxin-10, Cardiac Dysfunction, Fatty Acid Metabolism, Animals, Mice
Source:Molecular Metabolism
Page Range:67-78
Date:February 2016
Additional Information:Erratum in: Mol Metab 35: 100970.
Official Publication:https://doi.org/10.1016/j.molmet.2015.11.004
PubMed:View item in PubMed

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