title: Ataxin-10 is part of a cachexokine cocktail triggering cardiac metabolic dysfunction in cancer cachexia.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, 85764 Neuherberg, Germany; Joint Heidelberg-IDC Translational Diabetes Program, Inner Medicine I, Heidelberg University Hospital, 69120 Heidelberg, Germany; DZHK (German Centre for Cardiovascular Research), Partner site Heidelberg/Mannheim, 69120 Heidelberg, Germany; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Schäfer
authors.affiliation: Department of Cardiology, Angiology and Pulmonology, University Hospital Heidelberg, 69120 Heidelberg, Germany; DZHK (German Centre for Cardiovascular Research), Partner site Heidelberg/Mannheim, 69120 Heidelberg, Germany; Department of Molecular Cardiology and Epigenetics, University Hospital Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Christian U
authors.initials: CU
authors.lastname: Oeing
authors.affiliation: Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, 85764 Neuherberg, Germany; Joint Heidelberg-IDC Translational Diabetes Program, Inner Medicine I, Heidelberg University Hospital, 69120 Heidelberg, Germany; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Rohm
authors.affiliation: Department of Cardiology, Angiology and Pulmonology, University Hospital Heidelberg, 69120 Heidelberg, Germany; DZHK (German Centre for Cardiovascular Research), Partner site Heidelberg/Mannheim, 69120 Heidelberg, Germany; Department of Molecular Cardiology and Epigenetics, University Hospital Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Ezgi
authors.initials: E
authors.lastname: Baysal-Temel
authors.affiliation: Department of Cardiology, Angiology and Pulmonology, University Hospital Heidelberg, 69120 Heidelberg, Germany; DZHK (German Centre for Cardiovascular Research), Partner site Heidelberg/Mannheim, 69120 Heidelberg, Germany; Department of Molecular Cardiology and Epigenetics, University Hospital Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Lorenz H
authors.initials: LH
authors.lastname: Lehmann
authors.affiliation: Department of Cardiology, Angiology and Pulmonology, University Hospital Heidelberg, 69120 Heidelberg, Germany; DZHK (German Centre for Cardiovascular Research), Partner site Heidelberg/Mannheim, 69120 Heidelberg, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Bauer
authors.affiliation: Division of Signaling and Functional Genomics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; DZHK (German Centre for Cardiovascular Research), Partner site Heidelberg/Mannheim, 69120 Heidelberg, Germany.
authors.forename: H Christian
authors.initials: HC
authors.lastname: Volz
authors.affiliation: Division of Signaling and Functional Genomics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; DZHK (German Centre for Cardiovascular Research), Partner site Heidelberg/Mannheim, 69120 Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Boutros
authors.affiliation: Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, 85764 Neuherberg, Germany; Joint Heidelberg-IDC Translational Diabetes Program, Inner Medicine I, Heidelberg University Hospital, 69120 Heidelberg, Germany; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Sohn
authors.affiliation: Center for Medical Research, University of Mannheim, 68167 Mannheim, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Sticht
authors.affiliation: Center for Medical Research, University of Mannheim, 68167 Mannheim, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Gretz
authors.affiliation: Department for Cell Signaling and Mass Spectrometry, Max Delbrück Center, 13092 Berlin, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Eichelbaum
authors.affiliation: Department of Experimental and Clinical Pharmacology and Toxicology, University Medical Center, 20246 Hamburg-Eppendorf, Germany; DZHK (German Centre for Cardiovascular Research), Partner site Hamburg/Kiel/Lübeck, 20246 Hamburg-Eppendorf, Germany.
authors.forename: Tessa
authors.initials: T
authors.lastname: Werner
authors.affiliation: Department of Experimental and Clinical Pharmacology and Toxicology, University Medical Center, 20246 Hamburg-Eppendorf, Germany; DZHK (German Centre for Cardiovascular Research), Partner site Hamburg/Kiel/Lübeck, 20246 Hamburg-Eppendorf, Germany.
authors.forename: Marc N
authors.initials: MN
authors.lastname: Hirt
authors.affiliation: Department of Experimental and Clinical Pharmacology and Toxicology, University Medical Center, 20246 Hamburg-Eppendorf, Germany; DZHK (German Centre for Cardiovascular Research), Partner site Hamburg/Kiel/Lübeck, 20246 Hamburg-Eppendorf, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Eschenhagen
authors.affiliation: Core Facility Tumor Models, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Müller-Decker
authors.affiliation: Department of General Surgery, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Strobel
authors.affiliation: Department of General Surgery, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Thilo
authors.initials: T
authors.lastname: Hackert
authors.affiliation: Genome Biology Unit, EMBL, 69117 Heidelberg, Germany.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Krijgsveld
authors.affiliation: Department of Cardiology, Angiology and Pulmonology, University Hospital Heidelberg, 69120 Heidelberg, Germany; DZHK (German Centre for Cardiovascular Research), Partner site Heidelberg/Mannheim, 69120 Heidelberg, Germany.
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.affiliation: Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, 85764 Neuherberg, Germany; Joint Heidelberg-IDC Translational Diabetes Program, Inner Medicine I, Heidelberg University Hospital, 69120 Heidelberg, Germany; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Berriel Diaz
authors.affiliation: Department of Cardiology, Angiology and Pulmonology, University Hospital Heidelberg, 69120 Heidelberg, Germany; DZHK (German Centre for Cardiovascular Research), Partner site Heidelberg/Mannheim, 69120 Heidelberg, Germany; Department of Molecular Cardiology and Epigenetics, University Hospital Heidelberg, 69120 Heidelberg, Germany. Electronic address: johannes.backs@med.uni-heidelberg.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: Backs
authors.affiliation: Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, 85764 Neuherberg, Germany; Joint Heidelberg-IDC Translational Diabetes Program, Inner Medicine I, Heidelberg University Hospital, 69120 Heidelberg, Germany; DZHK (German Centre for Cardiovascular Research), Partner site Heidelberg/Mannheim, 69120 Heidelberg, Germany; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany. Electronic address: stephan.herzig@helmholtz-muenchen.de.
authors.forename: Stephan
authors.initials: S
authors.lastname: Herzig
keywords: Ataxin-10; Cancer cachexia; Cardiac dysfunction; Fatty acid metabolism