Ataxin-10 is part of a cachexokine cocktail triggering cardiac metabolic dysfunction in cancer cachexia
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 most...
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| Main Authors: | , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article (Journal) |
| Language: | English |
| Published: |
February 2016
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| In: |
Molecular metabolism
Year: 2016, Volume: 5, Issue: 2, Pages: 67-78 |
| ISSN: | 2212-8778 |
| DOI: | 10.1016/j.molmet.2015.11.004 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1016/j.molmet.2015.11.004 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S2212877815002161 
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| Author Notes: | 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 |
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| 520 | |a 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. | ||
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| 650 | 4 | |a Cancer cachexia | |
| 650 | 4 | |a Cardiac dysfunction | |
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