mTORC2 interactome and localization determine aggressiveness of high-grade glioma cells through association with gelsolin
Abstract mTOR complex 2 (mTORC2) has been implicated as a key regulator of glioblastoma cell migration. However, the roles of mTORC2 in the migrational control process have not been entirely elucidated. Here, we elaborate that active mTORC2 is crucial for GBM cell motility. Inhibition of mTORC2 impa...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-33872-y |
| _version_ | 1827956757351104512 |
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| author | Naphat Chantaravisoot Piriya Wongkongkathep Nuttiya Kalpongnukul Narawit Pacharakullanon Pornchai Kaewsapsak Chaiyaboot Ariyachet Joseph A. Loo Fuyuhiko Tamanoi Trairak Pisitkun |
| author_facet | Naphat Chantaravisoot Piriya Wongkongkathep Nuttiya Kalpongnukul Narawit Pacharakullanon Pornchai Kaewsapsak Chaiyaboot Ariyachet Joseph A. Loo Fuyuhiko Tamanoi Trairak Pisitkun |
| author_sort | Naphat Chantaravisoot |
| collection | DOAJ |
| description | Abstract mTOR complex 2 (mTORC2) has been implicated as a key regulator of glioblastoma cell migration. However, the roles of mTORC2 in the migrational control process have not been entirely elucidated. Here, we elaborate that active mTORC2 is crucial for GBM cell motility. Inhibition of mTORC2 impaired cell movement and negatively affected microfilament and microtubule functions. We also aimed to characterize important players involved in the regulation of cell migration and other mTORC2-mediated cellular processes in GBM cells. Therefore, we quantitatively characterized the alteration of the mTORC2 interactome under selective conditions using affinity purification-mass spectrometry in glioblastoma. We demonstrated that changes in cell migration ability specifically altered mTORC2-associated proteins. GSN was identified as one of the most dynamic proteins. The mTORC2-GSN linkage was mostly highlighted in high-grade glioma cells, connecting functional mTORC2 to multiple proteins responsible for directional cell movement in GBM. Loss of GSN disconnected mTORC2 from numerous cytoskeletal proteins and affected the membrane localization of mTORC2. In addition, we reported 86 stable mTORC2-interacting proteins involved in diverse molecular functions, predominantly cytoskeletal remodeling, in GBM. Our findings might help expand future opportunities for predicting the highly migratory phenotype of brain cancers in clinical investigations. |
| first_indexed | 2024-04-09T15:09:51Z |
| format | Article |
| id | doaj.art-815f784b35444254bad458b722957adf |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T15:09:51Z |
| publishDate | 2023-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-815f784b35444254bad458b722957adf2023-04-30T11:17:26ZengNature PortfolioScientific Reports2045-23222023-04-0113112010.1038/s41598-023-33872-ymTORC2 interactome and localization determine aggressiveness of high-grade glioma cells through association with gelsolinNaphat Chantaravisoot0Piriya Wongkongkathep1Nuttiya Kalpongnukul2Narawit Pacharakullanon3Pornchai Kaewsapsak4Chaiyaboot Ariyachet5Joseph A. Loo6Fuyuhiko Tamanoi7Trairak Pisitkun8Department of Biochemistry, Faculty of Medicine, Chulalongkorn UniversityCenter of Excellence in Systems Biology, Faculty of Medicine, Chulalongkorn UniversityCenter of Excellence in Systems Biology, Faculty of Medicine, Chulalongkorn UniversityDepartment of Biochemistry, Faculty of Medicine, Chulalongkorn UniversityDepartment of Biochemistry, Faculty of Medicine, Chulalongkorn UniversityDepartment of Biochemistry, Faculty of Medicine, Chulalongkorn UniversityDepartment of Chemistry and Biochemistry, University of CaliforniaDepartment of Microbiology, Immunology and Molecular Genetics, University of CaliforniaCenter of Excellence in Systems Biology, Faculty of Medicine, Chulalongkorn UniversityAbstract mTOR complex 2 (mTORC2) has been implicated as a key regulator of glioblastoma cell migration. However, the roles of mTORC2 in the migrational control process have not been entirely elucidated. Here, we elaborate that active mTORC2 is crucial for GBM cell motility. Inhibition of mTORC2 impaired cell movement and negatively affected microfilament and microtubule functions. We also aimed to characterize important players involved in the regulation of cell migration and other mTORC2-mediated cellular processes in GBM cells. Therefore, we quantitatively characterized the alteration of the mTORC2 interactome under selective conditions using affinity purification-mass spectrometry in glioblastoma. We demonstrated that changes in cell migration ability specifically altered mTORC2-associated proteins. GSN was identified as one of the most dynamic proteins. The mTORC2-GSN linkage was mostly highlighted in high-grade glioma cells, connecting functional mTORC2 to multiple proteins responsible for directional cell movement in GBM. Loss of GSN disconnected mTORC2 from numerous cytoskeletal proteins and affected the membrane localization of mTORC2. In addition, we reported 86 stable mTORC2-interacting proteins involved in diverse molecular functions, predominantly cytoskeletal remodeling, in GBM. Our findings might help expand future opportunities for predicting the highly migratory phenotype of brain cancers in clinical investigations.https://doi.org/10.1038/s41598-023-33872-y |
| spellingShingle | Naphat Chantaravisoot Piriya Wongkongkathep Nuttiya Kalpongnukul Narawit Pacharakullanon Pornchai Kaewsapsak Chaiyaboot Ariyachet Joseph A. Loo Fuyuhiko Tamanoi Trairak Pisitkun mTORC2 interactome and localization determine aggressiveness of high-grade glioma cells through association with gelsolin Scientific Reports |
| title | mTORC2 interactome and localization determine aggressiveness of high-grade glioma cells through association with gelsolin |
| title_full | mTORC2 interactome and localization determine aggressiveness of high-grade glioma cells through association with gelsolin |
| title_fullStr | mTORC2 interactome and localization determine aggressiveness of high-grade glioma cells through association with gelsolin |
| title_full_unstemmed | mTORC2 interactome and localization determine aggressiveness of high-grade glioma cells through association with gelsolin |
| title_short | mTORC2 interactome and localization determine aggressiveness of high-grade glioma cells through association with gelsolin |
| title_sort | mtorc2 interactome and localization determine aggressiveness of high grade glioma cells through association with gelsolin |
| url | https://doi.org/10.1038/s41598-023-33872-y |
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