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

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

Molecular metabolism (2016-02-26)
Michaela Schäfer, Christian U Oeing, Maria Rohm, Ezgi Baysal-Temel, Lorenz H Lehmann, Ralf Bauer, H Christian Volz, Michael Boutros, Daniela Sohn, Carsten Sticht, Norbert Gretz, Katrin Eichelbaum, Tessa Werner, Marc N Hirt, Thomas Eschenhagen, Karin Müller-Decker, Oliver Strobel, Thilo Hackert, Jeroen Krijgsveld, Hugo A Katus, Mauricio Berriel Diaz, Johannes Backs, Stephan Herzig
ABSTRACT

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. 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. 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.

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Sodium palmitate, ≥98.5%