Glioblastoma-derived migrasomes promote migration and invasion by releasing PAK4 and LAMA4
Abstract Almost all high-grade gliomas, particularly glioblastoma (GBM), are highly migratory and aggressive. Migrasomes are organelles produced by highly migratory cells capable of mediating intercellular communication. Thus, GBM cells may produce migrasomes during migration. However, it remains un...
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Nature Portfolio
2025-01-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07526-w |
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| author | Zhe Huang Ming Wang Yitian Chen Hua Tang Kuo Tang Mingkuan Zhao Wei Yang Zhengjun Zhou Junjie Tian Wei Xiang Shenjie Li Qinglian Luo Luotong Liu Yanru Zhao Tao Li Jie Zhou Ligang Chen |
| author_facet | Zhe Huang Ming Wang Yitian Chen Hua Tang Kuo Tang Mingkuan Zhao Wei Yang Zhengjun Zhou Junjie Tian Wei Xiang Shenjie Li Qinglian Luo Luotong Liu Yanru Zhao Tao Li Jie Zhou Ligang Chen |
| author_sort | Zhe Huang |
| collection | DOAJ |
| description | Abstract Almost all high-grade gliomas, particularly glioblastoma (GBM), are highly migratory and aggressive. Migrasomes are organelles produced by highly migratory cells capable of mediating intercellular communication. Thus, GBM cells may produce migrasomes during migration. However, it remains unclear whether migrasomes can influence GBM migration and invasion. In this study, we observed the presence and formation of migrasomes in GBM cells. We found that expression levels of key migrasome formation factor, tetraspanin 4 (TSPAN4), correlated positively with pathological grade and poor prognosis of GBM based on the databases and clinical samples analysis. Subsequently, we knocked down TSPAN4 and found that GBM cell migration and invasion were significantly inhibited due to the reduced formation of migrasomes. We further confirmed that migrasomes are enriched in extracellular matrix (ECM)-related proteins such as p21-activating kinase 4 (PAK4) and laminin alpha 4 (LAMA4). Our experimental results suggest that migrasomes promote GBM cells migration by releasing such proteins into the extracellular space. Overall, we identified migrasomes in GBM and the molecular mechanisms by which they regulate them, providing potential targets for treating GBM. |
| format | Article |
| id | doaj-art-846d18407cd3438d8572afea7b673f2f |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-846d18407cd3438d8572afea7b673f2f2025-01-26T12:48:10ZengNature PortfolioCommunications Biology2399-36422025-01-018111410.1038/s42003-025-07526-wGlioblastoma-derived migrasomes promote migration and invasion by releasing PAK4 and LAMA4Zhe Huang0Ming Wang1Yitian Chen2Hua Tang3Kuo Tang4Mingkuan Zhao5Wei Yang6Zhengjun Zhou7Junjie Tian8Wei Xiang9Shenjie Li10Qinglian Luo11Luotong Liu12Yanru Zhao13Tao Li14Jie Zhou15Ligang Chen16Department of Neurosurgery, The Affiliated Hospital, Southwest Medical UniversityDepartment of Neurosurgery, The Affiliated Hospital, Southwest Medical UniversityFaculty of Health Sciences, University of MacauDepartment of Neurosurgery, The People’s Hospital of Jianyang CityLaboratory of Mitochondrial Metabolism and Perioperative Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan UniversityDepartment of Neurosurgery, The Affiliated Hospital, Southwest Medical UniversityLaboratory of Mitochondrial Metabolism and Perioperative Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan UniversityDepartment of Neurosurgery, The Affiliated Hospital, Southwest Medical UniversityDepartment of Neurosurgery, The Affiliated Hospital, Southwest Medical UniversityDepartment of Neurosurgery, The Affiliated Hospital, Southwest Medical UniversityDepartment of Neurosurgery, The Affiliated Hospital, Southwest Medical UniversityDepartment of Neurosurgery, The Affiliated Hospital, Southwest Medical UniversityDepartment of Neurosurgery, The Affiliated Hospital, Southwest Medical UniversityDepartment of Neurosurgery, The Affiliated Hospital, Southwest Medical UniversityLaboratory of Mitochondrial Metabolism and Perioperative Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan UniversityDepartment of Neurosurgery, The Affiliated Hospital, Southwest Medical UniversityDepartment of Neurosurgery, The Affiliated Hospital, Southwest Medical UniversityAbstract Almost all high-grade gliomas, particularly glioblastoma (GBM), are highly migratory and aggressive. Migrasomes are organelles produced by highly migratory cells capable of mediating intercellular communication. Thus, GBM cells may produce migrasomes during migration. However, it remains unclear whether migrasomes can influence GBM migration and invasion. In this study, we observed the presence and formation of migrasomes in GBM cells. We found that expression levels of key migrasome formation factor, tetraspanin 4 (TSPAN4), correlated positively with pathological grade and poor prognosis of GBM based on the databases and clinical samples analysis. Subsequently, we knocked down TSPAN4 and found that GBM cell migration and invasion were significantly inhibited due to the reduced formation of migrasomes. We further confirmed that migrasomes are enriched in extracellular matrix (ECM)-related proteins such as p21-activating kinase 4 (PAK4) and laminin alpha 4 (LAMA4). Our experimental results suggest that migrasomes promote GBM cells migration by releasing such proteins into the extracellular space. Overall, we identified migrasomes in GBM and the molecular mechanisms by which they regulate them, providing potential targets for treating GBM.https://doi.org/10.1038/s42003-025-07526-w |
| spellingShingle | Zhe Huang Ming Wang Yitian Chen Hua Tang Kuo Tang Mingkuan Zhao Wei Yang Zhengjun Zhou Junjie Tian Wei Xiang Shenjie Li Qinglian Luo Luotong Liu Yanru Zhao Tao Li Jie Zhou Ligang Chen Glioblastoma-derived migrasomes promote migration and invasion by releasing PAK4 and LAMA4 Communications Biology |
| title | Glioblastoma-derived migrasomes promote migration and invasion by releasing PAK4 and LAMA4 |
| title_full | Glioblastoma-derived migrasomes promote migration and invasion by releasing PAK4 and LAMA4 |
| title_fullStr | Glioblastoma-derived migrasomes promote migration and invasion by releasing PAK4 and LAMA4 |
| title_full_unstemmed | Glioblastoma-derived migrasomes promote migration and invasion by releasing PAK4 and LAMA4 |
| title_short | Glioblastoma-derived migrasomes promote migration and invasion by releasing PAK4 and LAMA4 |
| title_sort | glioblastoma derived migrasomes promote migration and invasion by releasing pak4 and lama4 |
| url | https://doi.org/10.1038/s42003-025-07526-w |
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