| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2016 |
| Předmět: |
|
| Zdroj: |
Molecular Metabolism, Vol 5, Iss 2, Pp 67-78 (2016) |
| Druh dokumentu: |
article |
| ISSN: |
2212-8778 |
| DOI: |
10.1016/j.molmet.2015.11.004 |
| Popis: |
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. Author Video: Author Video Watch what authors say about their articles Keywords: Cancer cachexia, Ataxin-10, Cardiac dysfunction, Fatty acid metabolism |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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