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Host autophagy mediates organ wasting and nutrient mobilization for tumor growth
Author(s) -
Khezri Rojyar,
Holland Petter,
Schoborg Todd Andrew,
Abramovich Ifat,
Takáts Szabolcs,
Dillard Caroline,
Jain Ashish,
O'Farrell Fergal,
Schultz Sebastian Wolfgang,
Hagopian William M,
Quintana Eduardo Martin,
Ng Rachel,
Katheder Nadja Sandra,
Rahman Mohammed Mahidur,
Teles Reis José Gerardo,
Brech Andreas,
Jasper Heinrich,
Rusan Nasser M,
Jahren Anne Hope,
Gottlieb Eyal,
Rusten Tor Erik
Publication year - 2021
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2020107336
Subject(s) - biology , autophagy , wasting , host (biology) , mobilization , microbiology and biotechnology , nutrient , ecology , genetics , biochemistry , apoptosis , history , archaeology
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 Ras V12 ; 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.