Abstract 3534: Protein acylation mediates encapsulation of Src kinase into exosomes

Exosomes are nanosized vesicles (30-150 nm) secreted from almost all cell types (1). Exosomes play important roles in cell-cell communication through the transfer of exosomal proteins, mRNA, and microRNAs, mediating immune escape and promoting tumor progression (2,3). However, it remains unclear how oncogenic proteins are selectively disseminated through exosomes. Myristoylation is lipid modification of protein involved in the attachment of N-terminal glycine of proteins with a myristoyl group. It is critical for various biologic functions including cell signaling, protein localization, and cell-cell communication (4). In this study, we evaluated the role of protein acylation for the encapsulation of Src family kinases in exosomes. Myristoylation promotes the enrichment of Src kinase in exosomes whereas palmitoylation inhibits the encapsulation process. Additionally, phosphorylated Src protein was more favored to be capsulated in exosomes. Mechanistically, knockdown of TSG101 decreased expression levels of Src kinase in exosomes, indicating that Src encapsulation into exosomes is associated with endosomal sorting complexes required for transport (ESCRT). Finally, Src kinase can be translocated to normal cells via exosomes cargo to induce pathologic signaling. These results provide new insights of Src kinase encapsulation mechanism into exosomes, and therapeutic approaches for inhibiting the transfer of oncogenic proteins through targeting protein myristoylation process. References: 1. Simons M, Raposo G. Exosomes–vesicular carriers for intercellular communication. Curr Opin Cell Biol 2009;21(4):575-81. 2. Skog J et al. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nature Cell Biol 2008;10(12):1470-6. 3. Abusamra AJ et al. Tumor exosomes expressing Fas ligand mediate CD8+ T-cell apoptosis. Blood Cells Mol Dis 2005;35(2):169-73. 4. Casey PJ. Protein lipidation in cell signaling. Science 1995;268(5208):221. Citation Format: Ru Wen, Qianjin Li, Sungjin Kim, Yongjie Ma, Jin Xie, Houjian Cai. Protein acylation mediates encapsulation of Src kinase into exosomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3534.