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N-acetylglucosaminyltransferase-V (GnT-V)-enriched small extracellular vesicles mediate N-glycan remodeling in recipient cells
Small extracellular vesicles (sEVs) secreted from cancer cells play pivotal roles in cancer metastasis and malignancy by transferring biomolecules and conditioning future metastatic sites. Studies have elucidated structures and functions of glycans on sEVs; however, whether sEVs remodel glycans in r...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9794981/ https://www.ncbi.nlm.nih.gov/pubmed/36590176 http://dx.doi.org/10.1016/j.isci.2022.105747 |
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author | Hirata, Tetsuya Harada, Yoichiro Hirosawa, Koichiro M. Tokoro, Yuko Suzuki, Kenichi G.N. Kizuka, Yasuhiko |
author_facet | Hirata, Tetsuya Harada, Yoichiro Hirosawa, Koichiro M. Tokoro, Yuko Suzuki, Kenichi G.N. Kizuka, Yasuhiko |
author_sort | Hirata, Tetsuya |
collection | PubMed |
description | Small extracellular vesicles (sEVs) secreted from cancer cells play pivotal roles in cancer metastasis and malignancy by transferring biomolecules and conditioning future metastatic sites. Studies have elucidated structures and functions of glycans on sEVs; however, whether sEVs remodel glycans in recipient cells remains poorly understood. Here, we examined the enzyme activity of glycosyltransferases for complex N-glycan biosynthesis in cancer-derived sEVs and discovered that cancer-related glycosyltransferase, N-acetylglucosaminyltransferase-V (GnT-V, a.k.a. MGAT5), is selectively enriched in sEVs among various glycosyltransferases. GnT-V in sEVs is a cleaved form, and cleavage by SPPL3 protease is necessary for loading GnT-V in sEVs. Fractionation experiments and single-particle imaging further revealed that GnT-V was enriched in non-exosomal sEVs. Strikingly, we found that enzymatically active GnT-V in sEVs was transferred to recipient cells and the N-glycan structures of recipient cells were remodeled to express GnT-V-produced glycans. Our results suggest GnT-V-enriched sEVs’ role in glycan remodeling in cancer metastasis. |
format | Online Article Text |
id | pubmed-9794981 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-97949812022-12-29 N-acetylglucosaminyltransferase-V (GnT-V)-enriched small extracellular vesicles mediate N-glycan remodeling in recipient cells Hirata, Tetsuya Harada, Yoichiro Hirosawa, Koichiro M. Tokoro, Yuko Suzuki, Kenichi G.N. Kizuka, Yasuhiko iScience Article Small extracellular vesicles (sEVs) secreted from cancer cells play pivotal roles in cancer metastasis and malignancy by transferring biomolecules and conditioning future metastatic sites. Studies have elucidated structures and functions of glycans on sEVs; however, whether sEVs remodel glycans in recipient cells remains poorly understood. Here, we examined the enzyme activity of glycosyltransferases for complex N-glycan biosynthesis in cancer-derived sEVs and discovered that cancer-related glycosyltransferase, N-acetylglucosaminyltransferase-V (GnT-V, a.k.a. MGAT5), is selectively enriched in sEVs among various glycosyltransferases. GnT-V in sEVs is a cleaved form, and cleavage by SPPL3 protease is necessary for loading GnT-V in sEVs. Fractionation experiments and single-particle imaging further revealed that GnT-V was enriched in non-exosomal sEVs. Strikingly, we found that enzymatically active GnT-V in sEVs was transferred to recipient cells and the N-glycan structures of recipient cells were remodeled to express GnT-V-produced glycans. Our results suggest GnT-V-enriched sEVs’ role in glycan remodeling in cancer metastasis. Elsevier 2022-12-06 /pmc/articles/PMC9794981/ /pubmed/36590176 http://dx.doi.org/10.1016/j.isci.2022.105747 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Hirata, Tetsuya Harada, Yoichiro Hirosawa, Koichiro M. Tokoro, Yuko Suzuki, Kenichi G.N. Kizuka, Yasuhiko N-acetylglucosaminyltransferase-V (GnT-V)-enriched small extracellular vesicles mediate N-glycan remodeling in recipient cells |
title | N-acetylglucosaminyltransferase-V (GnT-V)-enriched small extracellular vesicles mediate N-glycan remodeling in recipient cells |
title_full | N-acetylglucosaminyltransferase-V (GnT-V)-enriched small extracellular vesicles mediate N-glycan remodeling in recipient cells |
title_fullStr | N-acetylglucosaminyltransferase-V (GnT-V)-enriched small extracellular vesicles mediate N-glycan remodeling in recipient cells |
title_full_unstemmed | N-acetylglucosaminyltransferase-V (GnT-V)-enriched small extracellular vesicles mediate N-glycan remodeling in recipient cells |
title_short | N-acetylglucosaminyltransferase-V (GnT-V)-enriched small extracellular vesicles mediate N-glycan remodeling in recipient cells |
title_sort | n-acetylglucosaminyltransferase-v (gnt-v)-enriched small extracellular vesicles mediate n-glycan remodeling in recipient cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9794981/ https://www.ncbi.nlm.nih.gov/pubmed/36590176 http://dx.doi.org/10.1016/j.isci.2022.105747 |
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