Cited 0 times in
Two distinct receptor-binding domains of human glycyl-tRNA synthetase 1 displayed on extracellular vesicles activate M1 polarization and phagocytic bridging of macrophages to cancer cells
DC Field | Value | Language |
---|---|---|
dc.date.accessioned | 2023-07-06T00:31:39Z | - |
dc.date.available | 2023-07-06T00:31:39Z | - |
dc.date.issued | 2020-07 | - |
dc.identifier.issn | 0304-3835 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/194851 | - |
dc.description.abstract | Macrophages play important roles in cancer microenvironment. Human cytosolic glycyl-tRNA synthetase (GARS1) was previously shown to be secreted via extracellular vesicles (EVs) from macrophages to trigger cancer cell death. However, the effects of GARS1-containing EVs (GARS1-EVs) on macrophages as well as on cancer cells and the working mechanisms of GARS1 in cancer microenvironment are not yet understood. Here we show that GARS1-EVs induce M1 polarization and facilitate phagocytosis of macrophages. GARS1-EVs triggers M1 polarization of macrophage via the specific interaction of the extracellular cadherin subdomains 1-4 of the cadherin EGF LAG seven-pass G-type receptor 2 (CELSR2) with the N-terminal WHEP domain containing peptide region of GARS1, and activates the RAF-MEK-ERK pathway for M1 type cytokine production and phagocytosis. Besides, GARS1 interacted with cadherin 6 (CDH6) of cancer cells via its C-terminal tRNA-binding domain to induce cancer cell death. In vivo model, GARS1-EVs showed potent suppressive activity against tumor initiation via M1 type macrophages. GARS1 displayed on macrophage-secreted extracellular vesicles suppressed tumor growth in dual mode, namely through pro-apoptotic effect on cancer cells and M1 polarization effect on macrophages. Collectively, these results elucidate the unique tumor suppressive activity and mechanism of GARS1-EVs by activating M1 macrophage via CELSR2 as well as by direct killing of cancer cells via CDH6. | - |
dc.description.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | Elsevier Science Ireland | - |
dc.relation.isPartOf | CANCER LETTERS | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Cadherins / metabolism | - |
dc.subject.MESH | Cell Polarity | - |
dc.subject.MESH | Extracellular Vesicles* / enzymology | - |
dc.subject.MESH | Extracellular Vesicles* / metabolism | - |
dc.subject.MESH | Glycine-tRNA Ligase* / analysis | - |
dc.subject.MESH | Glycine-tRNA Ligase* / metabolism | - |
dc.subject.MESH | Glycine-tRNA | - |
dc.subject.MESH | Ligase* / pharmacology | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Macrophages* / enzymology | - |
dc.subject.MESH | Macrophages* / metabolism | - |
dc.subject.MESH | Macrophages* / pathology | - |
dc.subject.MESH | Neoplasms* / enzymology | - |
dc.subject.MESH | Neoplasms* / metabolism | - |
dc.subject.MESH | Phagocytosis | - |
dc.subject.MESH | Tumor Microenvironment | - |
dc.title | Two distinct receptor-binding domains of human glycyl-tRNA synthetase 1 displayed on extracellular vesicles activate M1 polarization and phagocytic bridging of macrophages to cancer cells | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Others | - |
dc.contributor.googleauthor | Min Chul Park | - |
dc.contributor.googleauthor | Peter C Goughnour | - |
dc.contributor.googleauthor | Sangmi Jun | - |
dc.contributor.googleauthor | Seongmin Cho | - |
dc.contributor.googleauthor | Eunjoo Song | - |
dc.contributor.googleauthor | Sang Bum Kim | - |
dc.contributor.googleauthor | Hyeong Yun Kim | - |
dc.contributor.googleauthor | Jae Kyung Hyun | - |
dc.contributor.googleauthor | Pilhan Kim | - |
dc.contributor.googleauthor | Hyun Suk Jung | - |
dc.contributor.googleauthor | Sunghoon Kim | - |
dc.identifier.doi | 10.1016/j.canlet.2022.215698 | - |
dc.relation.journalcode | J00448 | - |
dc.identifier.eissn | 1872-7980 | - |
dc.identifier.pmid | 35523311 | - |
dc.identifier.url | https://www.sciencedirect.com/science/article/pii/S0304383522001823 | - |
dc.subject.keyword | Cadherin EGF LAG seven-pass G-type receptor 2 | - |
dc.subject.keyword | Cancer microenvironment | - |
dc.subject.keyword | Extracellular vesicles | - |
dc.subject.keyword | Glycyl-tRNA synthetase 1 | - |
dc.subject.keyword | Macrophage | - |
dc.citation.volume | 539 | - |
dc.citation.startPage | 215698 | - |
dc.identifier.bibliographicCitation | CANCER LETTERS, Vol.539 : 215698, 2020-07 | - |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.