MYC regulates metabolism through vesicular transfer of glycolytic kinases

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 interna...

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Autores principales:	Alexia Tsakaneli, Victor Corasolla Carregari, Martina Morini, Alessandra Eva, Giuliana Cangemi, Olesya Chayka, Evgeny Makarov, Sandra Bibbò, Emily Capone, Gianluca Sala, Vincenzo De Laurenzi, Evon Poon, Louis Chesler, Luisa Pieroni, Martin R. Larsen, Giuseppe Palmisano, Arturo Sala
Formato:	article
Lenguaje:	EN
Publicado:	The Royal Society 2021
Materias:	extracellular vesicles MYC MYCN neuroblastoma Warburg effect Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/12d0e9b553254367b95d2b65de857eae
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spelling	oai:doaj.org-article:12d0e9b553254367b95d2b65de857eae2021-12-01T08:06:04ZMYC regulates metabolism through vesicular transfer of glycolytic kinases10.1098/rsob.2102762046-2441https://doaj.org/article/12d0e9b553254367b95d2b65de857eae2021-12-01T00:00:00Zhttps://royalsocietypublishing.org/doi/10.1098/rsob.210276https://doaj.org/toc/2046-2441Amplification 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.Alexia TsakaneliVictor Corasolla CarregariMartina MoriniAlessandra EvaGiuliana CangemiOlesya ChaykaEvgeny MakarovSandra BibbòEmily CaponeGianluca SalaVincenzo De LaurenziEvon PoonLouis CheslerLuisa PieroniMartin R. LarsenGiuseppe PalmisanoArturo SalaThe Royal Societyarticleextracellular vesiclesMYCMYCNneuroblastomaWarburg effectBiology (General)QH301-705.5ENOpen Biology, Vol 11, Iss 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	extracellular vesicles MYC MYCN neuroblastoma Warburg effect Biology (General) QH301-705.5
spellingShingle	extracellular vesicles MYC MYCN neuroblastoma Warburg effect Biology (General) QH301-705.5 Alexia Tsakaneli Victor Corasolla Carregari Martina Morini Alessandra Eva Giuliana Cangemi Olesya Chayka Evgeny Makarov Sandra Bibbò Emily Capone Gianluca Sala Vincenzo De Laurenzi Evon Poon Louis Chesler Luisa Pieroni Martin R. Larsen Giuseppe Palmisano Arturo Sala MYC regulates metabolism through vesicular transfer of glycolytic kinases
description	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.
format	article
author	Alexia Tsakaneli Victor Corasolla Carregari Martina Morini Alessandra Eva Giuliana Cangemi Olesya Chayka Evgeny Makarov Sandra Bibbò Emily Capone Gianluca Sala Vincenzo De Laurenzi Evon Poon Louis Chesler Luisa Pieroni Martin R. Larsen Giuseppe Palmisano Arturo Sala
author_facet	Alexia Tsakaneli Victor Corasolla Carregari Martina Morini Alessandra Eva Giuliana Cangemi Olesya Chayka Evgeny Makarov Sandra Bibbò Emily Capone Gianluca Sala Vincenzo De Laurenzi Evon Poon Louis Chesler Luisa Pieroni Martin R. Larsen Giuseppe Palmisano Arturo Sala
author_sort	Alexia Tsakaneli
title	MYC regulates metabolism through vesicular transfer of glycolytic kinases
title_short	MYC regulates metabolism through vesicular transfer of glycolytic kinases
title_full	MYC regulates metabolism through vesicular transfer of glycolytic kinases
title_fullStr	MYC regulates metabolism through vesicular transfer of glycolytic kinases
title_full_unstemmed	MYC regulates metabolism through vesicular transfer of glycolytic kinases
title_sort	myc regulates metabolism through vesicular transfer of glycolytic kinases
publisher	The Royal Society
publishDate	2021
url	https://doaj.org/article/12d0e9b553254367b95d2b65de857eae
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MYC regulates metabolism through vesicular transfer of glycolytic kinases

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