title: The protein interaction network of extracellular vesicles derived from human colorectal cancer cells.
abstract: Various mammalian cells including tumor cells secrete extracellular vesicles (EVs), otherwise known as exosomes and microvesicles. EVs are nanosized bilayered proteolipids and play multiple roles in intercellular communication. Although many vesicular proteins have been identified, their functional interrelationships and the mechanisms of EV biogenesis remain unknown. By interrogating proteomic data using systems approaches, we have created a protein interaction network of human colorectal cancer cell-derived EVs which comprises 1491 interactions between 957 vesicular proteins. We discovered that EVs have well-connected clusters with several hub proteins similar to other subcellular networks. We also experimentally validated that direct protein interactions between cellular proteins may be involved in protein sorting during EV formation. Moreover, physically and functionally interconnected protein complexes form functional modules involved in EV biogenesis and functions. Specifically, we discovered that SRC signaling plays a major role in EV biogenesis, and confirmed that inhibition of SRC kinase decreased the intracellular biogenesis and cell surface release of EVs. Our study provides global insights into the cargo-sorting, biogenesis, and pathophysiological roles of these complex extracellular organelles.
authors.affiliation: Department of Life Science and Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea.
authors.forename: Dong-Sic
authors.initials: DS
authors.lastname: Choi
authors.forename: Jae-Seong
authors.initials: JS
authors.lastname: Yang
authors.forename: Eun-Jeong
authors.initials: EJ
authors.lastname: Choi
authors.forename: Su Chul
authors.initials: SC
authors.lastname: Jang
authors.forename: Solip
authors.initials: S
authors.lastname: Park
authors.forename: Oh Youn
authors.initials: OY
authors.lastname: Kim
authors.forename: Daehee
authors.initials: D
authors.lastname: Hwang
authors.forename: Kwang Pyo
authors.initials: KP
authors.lastname: Kim
authors.forename: Yoon-Keun
authors.initials: YK
authors.lastname: Kim
authors.forename: Sanguk
authors.initials: S
authors.lastname: Kim
authors.forename: Yong Song
authors.initials: YS
authors.lastname: Gho
mesh_terms: D016000:Cluster Analysis; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000378:metabolism; D055354:Exosomes / Q000737:chemistry* / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D009363:Neoplasm Proteins / Q000032:analysis* / Q000378:metabolism; D060066:Protein Interaction Maps; D020543:Proteome / Q000032:analysis* / Q000378:metabolism; D040901:Proteomics; D015203:Reproducibility of Results; D015398:Signal Transduction; D051176:beta Catenin / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: C495270:CTNNB1 protein, human; D009363:Neoplasm Proteins; D020543:Proteome; D051176:beta Catenin; D019061:src-Family Kinases