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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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Hauptverfasser: Schäfer, Michaela (VerfasserIn) , Oeing, Christian (VerfasserIn) , Rohm, Maria (VerfasserIn) , Baysal-Temel, Ezgi (VerfasserIn) , Lehmann, Lorenz (VerfasserIn) , Bauer, Ralf (VerfasserIn) , Sticht, Carsten (VerfasserIn) , Gretz, Norbert (VerfasserIn) , Strobel, Oliver (VerfasserIn) , Hackert, Thilo (VerfasserIn) , Katus, Hugo (VerfasserIn) , Berriel Diaz, Mauricio (VerfasserIn) , Backs, Johannes (VerfasserIn) , Herzig, Stephan (VerfasserIn)
Weitere Verfasser: Boutros, Michael (BerichterstatterIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: February 2016
In: Molecular metabolism
Year: 2016, Jahrgang: 5, Heft: 2, Pages: 67-78
ISSN:2212-8778
DOI:10.1016/j.molmet.2015.11.004
Online-Zugang:Verlag, Volltext: https://doi.org/10.1016/j.molmet.2015.11.004
Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S2212877815002161
Volltext
Verfasserangaben: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
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 22.10.2019
Beschreibung:Online Resource
ISSN:2212-8778
DOI:10.1016/j.molmet.2015.11.004

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