Open AccessMYC regulates metabolism through vesicular transfer of glycolytic kinases
Author(s) -
Alexia Tsakaneli,
Victor Corasolla Carregari,
Martina Morini,
Alessandra Eva,
Giuliana Cangemi,
Olesya Chayka,
Evgeny M. Makarov,
Sandra Bibbò,
Emily Capone,
Gianluca Sala,
Vincenzo De Laurenzi,
Evon Poon,
Louis Chesler,
Luisa Pieroni,
Martin R. Larsen,
Giuseppe Palmisano,
Arturo Sala
Publication year - 2021
Publication title -
open biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.078
H-Index - 53
ISSN - 2046-2441
DOI - 10.1098/rsob.210276
Subject(s) - neuroblastoma , biology , pkm2 , glycolysis , kinase , pyruvate kinase , cancer research , oncogene , cancer cell , warburg effect , hexokinase , n myc , cancer , microbiology and biotechnology , enzyme , cell culture , biochemistry , genetics , cell cycle , ganglioneuroma
Amplification of the proto-oncogeneMYCN 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.