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.
Pubmed ID: 36800996 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This monoclonal targets CD63
View all literature mentionsThis polyclonal targets Ki67 antibody - Proliferation Marker
View all literature mentionsThis monoclonal targets Cathepsin D antibody [CTD-19]
View all literature mentionsThis polyclonal targets TSG101
View all literature mentionsThis polyclonal targets FLAG
View all literature mentionsThis unknown targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis monoclonal targets tGFP
View all literature mentionsThis monoclonal targets EEA1
View all literature mentionsThis polyclonal targets IgG (H+L)
View all literature mentionsThis polyclonal targets Mouse IgG (H+L)
View all literature mentionsThis monoclonal targets GAPDH
View all literature mentionsThis polyclonal targets beta Actin
View all literature mentionsThis polyclonal targets alpha Tubulin
View all literature mentionsThis polyclonal targets p44/42 MAPK (Erk1/2)
View all literature mentionsThis monoclonal targets Phospho-p44/42 MAPK (Erk1/2) (Thr202/Tyr204)
View all literature mentionsThis monoclonal targets PXN
View all literature mentionsThis polyclonal targets Phospho-Paxillin (Tyr118)
View all literature mentionsThis monoclonal targets Src
View all literature mentionsThis monoclonal targets Phospho-Src Family (Tyr416) (D49G4) Rabbit mAb
View all literature mentionsThis monoclonal targets FAK
View all literature mentionsThis monoclonal targets Phospho-FAK (Tyr397) (D20B1) Rabbit mAb
View all literature mentionsThis monoclonal targets EGF Receptor
View all literature mentionsThis monoclonal targets ITGB5
View all literature mentionsThis monoclonal targets ITGB4
View all literature mentionsThis monoclonal targets Integrin beta1 (D2E5) Rabbit mAb
View all literature mentionsThis monoclonal targets Integrin αV
View all literature mentionsThis monoclonal targets HSC 70 (B-6)
View all literature mentionsThis monoclonal targets LC3B (D11) XP Rabbit mAb
View all literature mentionsThis monoclonal targets CANX
View all literature mentionsThis monoclonal targets HSP90AA1, HSP90AB1, HSP90B1
View all literature mentionsThis monoclonal targets LAMP1
View all literature mentionsThis monoclonal targets Flotillin-1 (C-2)
View all literature mentionsThis polyclonal targets VPS4A/B
View all literature mentionsThis monoclonal targets SDCBP
View all literature mentionsThis monoclonal targets Rab5
View all literature mentionsThis monoclonal targets Pdcd6ip
View all literature mentionsThis monoclonal targets Human CD63
View all literature mentions