期刊
EMBO JOURNAL
卷 39, 期 3, 页码 -出版社
WILEY
DOI: 10.15252/embj.2019102525
关键词
exosome; fatty acid oxidation; lipophagy; melanoma; obesity
资金
- Ligue Regionale Midi-Pyrenees contre le Cancer
- Fondation ARC pour la recherche sur le cancer
- Societe Francaise de Dermatologie
- Region Midi-Pyrenees
- European Found (FEDER)
- Toulouse Metropole
- French Ministry of Research with the program Investment for the Future, National Infrastructures for Biology and Health (ProFI, Proteomics French Infrastructure project) [ANR 10-INBS-08]
- Ligue nationale contre le Cancer
- Fondation de France [00081132]
Extracellular vesicles are emerging key actors in adipocyte communication. Notably, small extracellular vesicles shed by adipocytes stimulate fatty acid oxidation and migration in melanoma cells and these effects are enhanced in obesity. However, the vesicular actors and cellular processes involved remain largely unknown. Here, we elucidate the mechanisms linking adipocyte extracellular vesicles to metabolic remodeling and cell migration. We show that adipocyte vesicles stimulate melanoma fatty acid oxidation by providing both enzymes and substrates. In obesity, the heightened effect of extracellular vesicles depends on increased transport of fatty acids, not fatty acid oxidation-related enzymes. These fatty acids, stored within lipid droplets in cancer cells, drive fatty acid oxidation upon being released by lipophagy. This increase in mitochondrial activity redistributes mitochondria to membrane protrusions of migrating cells, which is necessary to increase cell migration in the presence of adipocyte vesicles. Our results provide key insights into the role of extracellular vesicles in the metabolic cooperation that takes place between adipocytes and tumors with particular relevance to obesity.
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