The Protein Interaction Network of Extracellular Vesicles Derived from Human Colorectal Cancer Cells
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- 作者：Dong-Sic Choi ; Jae-Seong Yang ; Eun-Jeong Choi ; Su Chul Jang ; Solip Park ; Oh Youn Kim ; Daehee Hwang ; Kwang Pyo Kim ; Yoon-Keun Kim ; Sanguk Kim ; Yong Song Gho
- 刊名：Journal of Proteome Research
- 出版年：2012
- 出版时间：February 3, 2012
- 年：2012
- 卷：11
- 期：2
- 页码：1144-1151
- 全文大小：509K
- 年卷期：v.11,no.2(February 3, 2012)
- ISSN：1535-3907
文摘
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.