MYC regulates metabolism through vesicular transfer of glycolytic kinases.
Open Biol
; 11(12): 210276, 2021 12.
Article
em En
| MEDLINE
| ID: mdl-34847775
Amplification of the proto-oncogene MYCN is a key molecular aberration in high-risk neuroblastoma and predictive of poor outcome in this childhood malignancy. We investigated the role of MYCN in regulating the protein cargo of extracellular vesicles (EVs) secreted by tumour cells that can be internalized by recipient cells with functional consequences. Using a switchable MYCN system coupled to mass spectrometry analysis, we found that MYCN regulates distinct sets of proteins in the EVs secreted by neuroblastoma cells. EVs produced by MYCN-expressing cells or isolated from neuroblastoma patients induced the Warburg effect, proliferation and c-MYC expression in target cells. Mechanistically, we linked the cancer-promoting activity of EVs to the glycolytic kinase pyruvate kinase M2 (PKM2) that was enriched in EVs secreted by MYC-expressing neuroblastoma cells. Importantly, the glycolytic enzymes PKM2 and hexokinase II were detected in the EVs circulating in the bloodstream of neuroblastoma patients, but not in those of non-cancer children. We conclude that MYC-activated cancers might spread oncogenic signals to remote body locations through EVs.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Hormônios Tireóideos
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Proteínas de Transporte
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Proteômica
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Vesículas Extracelulares
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Proteína Proto-Oncogênica N-Myc
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Hexoquinase
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Proteínas de Membrana
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Neuroblastoma
Tipo de estudo:
Prognostic_studies
Limite:
Child
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Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article