한빛사논문
- 조회450
Yu Jin Lee 1, Kyeong Jin Shin 1, Hyun-Jun Jang 1, Jin-Sun Ryu 2, Chae Young Lee 1, Jong Hyuk Yoon 3, Jeong Kon Seo 1, Sabin Park 4, Semin Lee 4, A Reum Je 5, Yang Hoon Huh 5, Sun-Young Kong 2,6, Taejoon Kwon 4, Pann-Ghill Suh 1,3, Young Chan Chae 1,7
1Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea
2Division of Translational Science, Research Institute and Hospital, National Cancer Center, Goyang 10408, Republic of Korea
3Korea Brain Research Institute (KBRI), Daegu 41062, Republic of Korea
4Department of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea
5Electron Microscopy Research Center, Korea Basic Science Institute (KBSI), Cheongju 28119, Republic of Korea
6Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang 10408, Republic of Korea
7Lead contact
Corresponding authors: Pann-Ghill Suh, Young Chan Chae
Abstract
Exosomes transport a variety of macromolecules and modulate intercellular communication in physiology and disease. However, the regulation mechanisms that determine exosome contents during exosome biogenesis remain poorly understood. Here, we find that GPR143, an atypical GPCR, controls the endosomal sorting complex required for the transport (ESCRT)-dependent exosome biogenesis pathway. GPR143 interacts with HRS (an ESCRT-0 Subunit) and promotes its association to cargo proteins, such as EGFR, which subsequently enables selective protein sorting into intraluminal vesicles (ILVs) in multivesicular bodies (MVBs). GPR143 is elevated in multiple cancers, and quantitative proteomic and RNA profiling of exosomes in human cancer cell lines showed that the GPR143-ESCRT pathway promotes secretion of exosomes that carry unique cargo, including integrins signaling proteins. Through gain- and loss-of-function studies in mice, we show that GPR143 promotes metastasis by secreting exosomes and increasing cancer cell motility/invasion through the integrin/FAK/Src pathway. These findings provide a mechanism for regulating the exosomal proteome and demonstrate its ability to promote cancer cell motility.
논문정보
- Research article
- 2023년 02월 (BRIC 등록일 2023-03-10)
- 국내 연구진
- 생명과학 > 노화/암생물학
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