title: Exosome proteomics reveals transcriptional regulator proteins with potential to mediate downstream pathways.
abstract: Exosomes are virus-sized, membrane-enclosed vesicles with origins in the cellular endosomal system, but are released extracellularly. As a population, these tiny vesicles carry relatively enormous amounts of information in their protein, lipid and nucleic acid content, and the vesicles can have profound impacts on recipient cells. This review employs publically-available data combined with gene ontology applications to propose a novel concept, that exosomes transport transcriptional and translational machinery that may have direct impacts on gene expression in recipient cells. Here, we examine the previously published proteomic contents of medulloblastoma-derived exosomes, focusing on transcriptional regulators; we found that there are numerous proteins that may have potential roles in transcriptional and translational regulation with putative influence on downstream, cancer-related pathways. We expanded this search to all of the proteins in the Vesiclepedia database; using gene ontology approaches, we see that these regulatory factors are implicated in many of the processes involved in cancer initiation and progression. This information suggests that some of the effects of exosomes on recipient cells may be due to the delivery of protein factors that can directly and fundamentally change the transcriptional landscape of the cells. Within a tumor environment, this has potential to tilt the advantage towards the cancer.
authors.affiliation: Department of Neurosurgery, University of Colorado School of Medicine, Aurora, Colorado, USA.
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Ung
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Madsen
authors.forename: Justin E
authors.initials: JE
authors.lastname: Hellwinkel
authors.forename: Alex M
authors.initials: AM
authors.lastname: Lencioni
authors.forename: Michael W
authors.initials: MW
authors.lastname: Graner
mesh_terms: D004268:DNA-Binding Proteins / Q000378:metabolism; D055354:Exosomes / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D020543:Proteome; D040901:Proteomics; D016601:RNA-Binding Proteins / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D020543:Proteome; D016601:RNA-Binding Proteins; D014157:Transcription Factors
keywords: Cancer; exosomes; gene ontology; proteomics; transcriptional regulators