Oncogene-regulated release of extracellular vesicles.

Abstract

Oncogenes can alter metabolism by changing the balance between anabolic and catabolic processes. However, how oncogenes regulate tumor cell biomass remains poorly understood. Using isogenic MCF10A cells transformed with nine different oncogenes, we show that specific oncogenes reduce the biomass of cancer cells by promoting extracellular vesicle (EV) release. While MYC and AURKB elicited the highest number of EVs, each oncogene selectively altered the protein composition of released EVs. Likewise, oncogenes alter secreted miRNAs. MYC-overexpressing cells require ceramide, whereas AURKB requires ESCRT to release high levels of EVs. We identify an inverse relationship between MYC upregulation and activation of the RAS/MEK/ERK signaling pathway for regulating EV release in some tumor cells. Finally, lysosome genes and activity are downregulated in the context of MYC and AURKB, suggesting that cellular contents, instead of being degraded, were released via EVs. Thus, oncogene-mediated biomass regulation via differential EV release is a new metabolic phenotype.

• Authors: Seda Kilinc, Rebekka Paisner, Roman Camarda, Suprit Gupta, Olga Momcilovic, Rebecca A Kohnz, Baris Avsaroglu, Noelle D L'Etoile, Rushika M Perera, Daniel K Nomura, Andrei Goga
• Journal: Developmental cell (Dev Cell) Vol. 56 Issue 13 Pg. 1989-2006.e6 (07 12 2021) ISSN: 1878-1551 [Electronic] United States
• PMID: 34118203 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• MYC protein, human
• Proto-Oncogene Proteins c-myc
• AURKB protein, human
• Aurora Kinase B
• MAP Kinase Kinase Kinases

Topics

• Aurora Kinase B (genetics)
• Energy Metabolism (genetics)
• Extracellular Vesicles (genetics, metabolism)
• Gene Expression Regulation, Neoplastic
• Genes, ras (genetics)
• Humans
• Lysosomes (genetics)
• MAP Kinase Kinase Kinases (genetics)
• MAP Kinase Signaling System (genetics)
• Metabolism (genetics)
• Oncogenes (genetics)
• Proto-Oncogene Proteins c-myc (genetics)
• Signal Transduction (genetics)