TGF‐β regulates the release of breast cancer cell‐derived extracellular vesicles and the sorting of their protein cargo by downregulating RAB27B expression
Abstract Extracellular vesicles (EVs) are important mediators of intercellular communication in the tumour microenvironment. The cytokine transforming growth factor‐β (TGF‐β) facilitates cancer progression via EVs secreted by cancer cells, which act on recipient cells in the tumour microenvironment....
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-12-01
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| Series: | Journal of Extracellular Vesicles |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/jev2.70026 |
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| _version_ | 1841525469989568512 |
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| author | Chao Li Agustin Enciso‐Martinez Roman I. Koning Mona Shahsavari Peter ten Dijke |
| author_facet | Chao Li Agustin Enciso‐Martinez Roman I. Koning Mona Shahsavari Peter ten Dijke |
| author_sort | Chao Li |
| collection | DOAJ |
| description | Abstract Extracellular vesicles (EVs) are important mediators of intercellular communication in the tumour microenvironment. The cytokine transforming growth factor‐β (TGF‐β) facilitates cancer progression via EVs secreted by cancer cells, which act on recipient cells in the tumour microenvironment. However, the mechanisms of how TGF‐β affects cancer cell EV release and composition are incompletely understood. Here, we systematically investigate the effects of TGF‐β on the release and protein composition of EVs from breast cancer cells. TGF‐β suppresses the transcription of RAB27B mediated by SMAD3 and thereby hampers EV release. Using click chemistry and quantitative proteomics, we found that TGF‐β increases the quantity of protein cargo and changes the composition of EVs by downregulating RAB27B expression. The recomposed EVs, induced by TGF‐β or RAB27B depletion, inhibit CD8+ T cell‐mediated breast cancer killing. Our findings reveal the critical roles of TGF‐β and RAB27B in cancer development by regulating EV release and composition and thus provide potential targets to improve cancer immunotherapy. |
| format | Article |
| id | doaj-art-8af9639346304c55aa248c274be4f44b |
| institution | Kabale University |
| issn | 2001-3078 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Extracellular Vesicles |
| spelling | doaj-art-8af9639346304c55aa248c274be4f44b2025-01-17T11:11:13ZengWileyJournal of Extracellular Vesicles2001-30782024-12-011312n/an/a10.1002/jev2.70026TGF‐β regulates the release of breast cancer cell‐derived extracellular vesicles and the sorting of their protein cargo by downregulating RAB27B expressionChao Li0Agustin Enciso‐Martinez1Roman I. Koning2Mona Shahsavari3Peter ten Dijke4Oncode Institute and Department of Cell and Chemical BiologyLeiden University Medical CenterLeidenNetherlandsOncode Institute and Department of Cell and Chemical BiologyLeiden University Medical CenterLeidenNetherlandsElectron Microscopy Facility, Department of Cell and Chemical BiologyLeiden University Medical CenterLeidenNetherlandsBiomedical Engineering & Physics; Laboratory of Experimental Clinical Chemistry, Laboratory Specialized Diagnostics & Research, Department of Laboratory MedicineAmsterdam University Medical Center, Meibergdreef 9 Amsterdam NetherlandsOncode Institute and Department of Cell and Chemical BiologyLeiden University Medical CenterLeidenNetherlandsAbstract Extracellular vesicles (EVs) are important mediators of intercellular communication in the tumour microenvironment. The cytokine transforming growth factor‐β (TGF‐β) facilitates cancer progression via EVs secreted by cancer cells, which act on recipient cells in the tumour microenvironment. However, the mechanisms of how TGF‐β affects cancer cell EV release and composition are incompletely understood. Here, we systematically investigate the effects of TGF‐β on the release and protein composition of EVs from breast cancer cells. TGF‐β suppresses the transcription of RAB27B mediated by SMAD3 and thereby hampers EV release. Using click chemistry and quantitative proteomics, we found that TGF‐β increases the quantity of protein cargo and changes the composition of EVs by downregulating RAB27B expression. The recomposed EVs, induced by TGF‐β or RAB27B depletion, inhibit CD8+ T cell‐mediated breast cancer killing. Our findings reveal the critical roles of TGF‐β and RAB27B in cancer development by regulating EV release and composition and thus provide potential targets to improve cancer immunotherapy.https://doi.org/10.1002/jev2.70026CD8+ T cellsextracellular vesiclesmultivesicular bodiesRAB27BreleaseTGF‐β |
| spellingShingle | Chao Li Agustin Enciso‐Martinez Roman I. Koning Mona Shahsavari Peter ten Dijke TGF‐β regulates the release of breast cancer cell‐derived extracellular vesicles and the sorting of their protein cargo by downregulating RAB27B expression Journal of Extracellular Vesicles CD8+ T cells extracellular vesicles multivesicular bodies RAB27B release TGF‐β |
| title | TGF‐β regulates the release of breast cancer cell‐derived extracellular vesicles and the sorting of their protein cargo by downregulating RAB27B expression |
| title_full | TGF‐β regulates the release of breast cancer cell‐derived extracellular vesicles and the sorting of their protein cargo by downregulating RAB27B expression |
| title_fullStr | TGF‐β regulates the release of breast cancer cell‐derived extracellular vesicles and the sorting of their protein cargo by downregulating RAB27B expression |
| title_full_unstemmed | TGF‐β regulates the release of breast cancer cell‐derived extracellular vesicles and the sorting of their protein cargo by downregulating RAB27B expression |
| title_short | TGF‐β regulates the release of breast cancer cell‐derived extracellular vesicles and the sorting of their protein cargo by downregulating RAB27B expression |
| title_sort | tgf β regulates the release of breast cancer cell derived extracellular vesicles and the sorting of their protein cargo by downregulating rab27b expression |
| topic | CD8+ T cells extracellular vesicles multivesicular bodies RAB27B release TGF‐β |
| url | https://doi.org/10.1002/jev2.70026 |
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