Multi-omics profiling of cachexia-targeted tissues reveals a spatio-temporally coordinated response to cancer
Cachexia is a wasting disorder associated with high morbidity and mortality in patients with cancer. Tumour-host interaction and maladaptive metabolic reprogramming are substantial, yet poorly understood, contributors to cachexia. Here we present a comprehensive overview of the spatio-temporal metabolic reprogramming during cachexia, using integrated metabolomics, RNA sequencing and <sup>13</sup>C-glucose tracing data from multiple tissues and tumours of C26 tumour-bearing male mice at different disease stages. We identified one-carbon metabolism as a tissue-overarching pathway characteristic for metabolic wasting in mice and patients and linked to inflammation, glucose hypermetabolism and atrophy in muscle. The same metabolic rewiring also occurred in five additional mouse models, namely Panc02, 8025, Apc<sup>Min</sup>, LLC and KPP, and a humanised cachexia mouse model. Together, our study provides a molecular framework for understanding metabolic reprogramming and the multi-tissue metabolite-coordinated response during cancer cachexia progression, with one-carbon metabolism as a tissue-overarching mechanism linked to wasting.
Authors
- H Hauner
- Dominik Lutter (ORCID: https://orcid.org/0000-0002-8800-0683)
- Radka Trubacova (ORCID: https://orcid.org/0000-0002-4619-2330)
- Olga Prokopchuk (ORCID: https://orcid.org/0000-0002-0697-512X)
- Kristýna Brejchová (ORCID: https://orcid.org/0000-0003-2839-6310)
- Tanja Krauss
- Ondřej Kuda (ORCID: https://orcid.org/0000-0001-7034-4536)
- Doris Kaltenecker (ORCID: https://orcid.org/0000-0002-4110-1006)
- Melina Claussnitzer (ORCID: https://orcid.org/0000-0003-2450-736X)
- Michaela Vondráčková (ORCID: https://orcid.org/0009-0005-6434-0201)
- Mauricio Berriel Díaz (ORCID: https://orcid.org/0000-0003-4670-919X)
- Pauline Morigny (ORCID: https://orcid.org/0000-0002-8001-7069)
- Claudine Seeliger (ORCID: https://orcid.org/0000-0002-7631-444X)
- Vignesh Karthikaisamy
- Maria Rohm (ORCID: https://orcid.org/0000-0003-3926-1534)
- Tuna Felix Samanci
- Stephan Herzig (ORCID: https://orcid.org/0000-0003-3950-3652)
- Marc E. Martignoni
- Konstantinos Makris (ORCID: https://orcid.org/0000-0002-9404-5706)
- H. Ji
- Sophia E. Chrysostomou
- Monika Krakovkova
- Anna Bidovec
- Mariana Ponce-de-Leon
- Su-Ping Ng
- Martina Schweiger
- Laure B. Bindels
Institutions
- Broad Institute (US)
- Harvard University (US)
- University of Graz (AT)
- Czech Academy of Sciences (CZ)
- Heidelberg University (DE)
- University Hospital Heidelberg (DE)
- TUM Klinikum (DE)
- Foundation Center (US)
- Helmholtz Zentrum München (DE)
- Weihenstephan-Triesdorf University of Applied Sciences (DE)
- Massachusetts General Hospital (US)
- Czech Academy of Sciences, Institute of Sociology (CZ)
- Novo Nordisk (United States) (US)
- BioTechMed-Graz (AT)
- German Centre for Cardiovascular Research (DE)
- Walloon Excellence in Lifesciences and Biotechnology (BE)
- Leibniz-Institute for Food Systems Biology at the Technical University of Munich (DE)
- Deutsches Diabetes-Zentrum e.V. (DE)
- German Center for Diabetes Research (DE)
- Heinrich Heine University Düsseldorf (DE)
- Technical University of Munich (DE)
- UCLouvain (BE)
Publication Details
- Journal
- Nature Metabolism
- Published
- 2026-01-15
- DOI
- https://doi.org/10.1038/s42255-025-01434-3
- Citations
- 4
- Primary Topic
- Nutrition and Health in Aging
- Type
- article
- Field-Weighted Citation Impact
- 131.36