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Status |
Public on May 06, 2020 |
Title |
Oncogene regulated release of extracellular vesicles |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Oncogenes reprogram multiple metabolic phenotypes of cancer cells including the balance between anabolic and catabolic processes, mechanisms of nutrient uptake, and choices in nutrient utilization. Here, we explore how different oncogenes regulate biomass loss via extracellular vesicle release. We use isogenic mammary breast epithelial cells transformed with a panel of oncogenes found commonly mutated, amplified or overexpressed in multiple cancers. We observe an increase in extracellular vesicle (EV) release upon oncogenic transformation, with MYC and AURKB oncogenes eliciting the highest number of EVs produced. Oncogene expression altered the protein composition of released EVs. Likewise, miRNAs were differentially sorted into EVs in an oncogene-specific manner. We performed an integrated pathway analysis of metabolites and gene expression across different oncogene-expressing cells and identified that ceramide-sphingosine metabolism was broadly deregulated, especially in MYC overexpressing cells. Inhibition of neutral sphingomyelinases (N-SMase) resulted in significant decrease in EV production in MYC high cells, while ESCRT-dependent small EV production predominated in AURKB cells.
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Overall design |
Gene expression analysis using RNA-seq from three different oncogene-expressing (MYC, AURKB, HRas) and control (Puro/Blast) MCF10A cells to identify dysregulated metabolic pathways that are important for extracelluler vesicle biogenesis
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Contributor(s) |
Goga A, Kilinc S |
Citation missing |
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Submission date |
May 06, 2019 |
Last update date |
May 06, 2020 |
Contact name |
Andrei Goga |
E-mail(s) |
andrei.goga@ucsf.edu
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Organization name |
UCSF
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Department |
Cell & Tissue Biology
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Lab |
Goga Lab
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Street address |
513 Parnassus Ave
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City |
San Francisco |
State/province |
CA |
ZIP/Postal code |
94143-0512 |
Country |
USA |
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Platforms (1) |
GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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Samples (12)
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Relations |
BioProject |
PRJNA541302 |
SRA |
SRP195601 |