Host autophagy mediates organ wasting and nutrient mobilization for tumor growth
| Autor: | Todd A. Schoborg, Eyal Gottlieb, Rachel K. Ng, Nadja Sandra Katheder, Nasser M. Rusan, Mohammed Mahidur Rahman, William M. Hagopian, Ashish Jain, José Gerardo Teles Reis, Szabolcs Takats, Tor Erik Rusten, Petter Holland, Ifat Abramovich, Rojyar Khezri, Caroline Dillard, Anne Hope Jahren, Eduardo Martin Quintana, Andreas Brech, Sebastian W. Schultz, Heinrich Jasper, Fergal O'Farrell |
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| Rok vydání: | 2021 |
| Předmět: |
autophagy
tumor Cachexia Anabolism muscle wasting Motility Biology Article General Biochemistry Genetics and Molecular Biology Neoplasms Organelle medicine Animals Humans Muscle Skeletal Molecular Biology Wasting Cancer chemistry.chemical_classification General Immunology and Microbiology General Neuroscience Autophagy Articles Nutrients Metabolism Muscle atrophy Cell biology Amino acid Disease Models Animal Drosophila melanogaster chemistry Disease Progression Drosophila Autophagy & Cell Death medicine.symptom Energy Metabolism cancer cachexia |
| Zdroj: | The EMBO Journal |
| ISSN: | 1460-2075 0261-4189 |
| Popis: | During tumor growth—when nutrient and anabolic demands are high—autophagy supports tumor metabolism and growth through lysosomal organelle turnover and nutrient recycling. Ras‐driven tumors additionally invoke non‐autonomous autophagy in the microenvironment to support tumor growth, in part through transfer of amino acids. Here we uncover a third critical role of autophagy in mediating systemic organ wasting and nutrient mobilization for tumor growth using a well‐characterized malignant tumor model in Drosophila melanogaster. Micro‐computed X‐ray tomography and metabolic profiling reveal that RasV12; scrib −/− tumors grow 10‐fold in volume, while systemic organ wasting unfolds with progressive muscle atrophy, loss of body mass, ‐motility, ‐feeding, and eventually death. Tissue wasting is found to be mediated by autophagy and results in host mobilization of amino acids and sugars into circulation. Natural abundance Carbon 13 tracing demonstrates that tumor biomass is increasingly derived from host tissues as a nutrient source as wasting progresses. We conclude that host autophagy mediates organ wasting and nutrient mobilization that is utilized for tumor growth. X‐ray tomography, metabolomics and carbon tracing reveal that autophagy‐mediated wasting of distal tissues provides amino acids and sugars that increase eye tumor biomass in Drosophila melanogaster. |
| Databáze: | OpenAIRE |
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