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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: Schäfer, Michaela (Author) , Oeing, Christian (Author) , Rohm, Maria (Author) , Baysal-Temel, Ezgi (Author) , Lehmann, Lorenz (Author) , Bauer, Ralf (Author) , Sticht, Carsten (Author) , Gretz, Norbert (Author) , Strobel, Oliver (Author) , Hackert, Thilo (Author) , Katus, Hugo (Author) , Berriel Diaz, Mauricio (Author) , Backs, Johannes (Author) , Herzig, Stephan (Author)
Other Authors: Boutros, Michael (Other)
Format: Article (Journal)
Language:English
Published: February 2016
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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Summary: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.
Item Description:Gesehen am 22.10.2019
Physical Description:Online Resource
ISSN:2212-8778
DOI:10.1016/j.molmet.2015.11.004

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