Multi-omics profiling of cachexia-targeted tissues reveals a spatio-temporally coordinated response to cancer

Abstract 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 13 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.…