MVK, induced by Kras, represses cGAS-Sting signalling in lung adenocarcinoma
Abstract Cholesterol metabolism is abnormally active in tumour cells. Metabolic enzymes related to cholesterol metabolism are upregulated in tumours, but their nonmetabolic functions remain unclear. We found that MVK (mevalonate kinase) is upregulated in lung adenocarcinoma tissues vs. normal tissue...
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| Format: | Article |
| Language: | English |
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BMC
2025-01-01
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| Series: | European Journal of Medical Research |
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| Online Access: | https://doi.org/10.1186/s40001-024-02186-8 |
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| _version_ | 1832585901651263488 |
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| author | Changsheng Zhou Jia Liu Xudong Hu Lu Lu Juan Hou Jian Wang Liqun Jiang Shuangshuang Huang Yu Lin Luyao Liu Lingling Cui Yiqian Liu Yufeng Huang |
| author_facet | Changsheng Zhou Jia Liu Xudong Hu Lu Lu Juan Hou Jian Wang Liqun Jiang Shuangshuang Huang Yu Lin Luyao Liu Lingling Cui Yiqian Liu Yufeng Huang |
| author_sort | Changsheng Zhou |
| collection | DOAJ |
| description | Abstract Cholesterol metabolism is abnormally active in tumour cells. Metabolic enzymes related to cholesterol metabolism are upregulated in tumours, but their nonmetabolic functions remain unclear. We found that MVK (mevalonate kinase) is upregulated in lung adenocarcinoma tissues vs. normal tissues and that its expression can be induced by constitutively activated Kras. By investigating the molecular mechanisms involved, we discovered that MVK interacts with TBK1, inhibiting TBK1 phosphorylation and thereby suppressing cGAS-Sting signalling. In addition, we found a negative correlation between MVK expression and CD8+ T-cell infiltration via a public database analysis. In summary, our study demonstrates the importance of the nonmetabolic function of MVK in modifying the immunological milieu and provides new targets for lung adenocarcinoma therapy. |
| format | Article |
| id | doaj-art-2be0bf88ab214185b21968b7c8567ea8 |
| institution | Kabale University |
| issn | 2047-783X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj-art-2be0bf88ab214185b21968b7c8567ea82025-01-26T12:21:43ZengBMCEuropean Journal of Medical Research2047-783X2025-01-0130111010.1186/s40001-024-02186-8MVK, induced by Kras, represses cGAS-Sting signalling in lung adenocarcinomaChangsheng Zhou0Jia Liu1Xudong Hu2Lu Lu3Juan Hou4Jian Wang5Liqun Jiang6Shuangshuang Huang7Yu Lin8Luyao Liu9Lingling Cui10Yiqian Liu11Yufeng Huang12Departments of Respiratory and Critical Care Medicine, The Affiliated Cangnan Hospital of Wenzhou Medical UniversityDepartment of Clinical Laboratory, Jingjiang People’s Hospital Affiliated With Yangzhou UniversityShanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of MedicineDepartments of Respiratory and Critical Care Medicine, The Affiliated Cangnan Hospital of Wenzhou Medical UniversityDepartment of Oncology, Jingjiang People’s Hospital Affiliated With Yangzhou UniversityDepartments of Respiratory and Critical Care Medicine, The Affiliated Cangnan Hospital of Wenzhou Medical UniversityDepartment of Thoracic Surgery, Jingjiang People’s Hospital Affiliated With Yangzhou UniversityDepartments of Respiratory and Critical Care Medicine, The Affiliated Cangnan Hospital of Wenzhou Medical UniversityDepartment of Oncology, the Affiliated Suzhou Hospital of Nanjing Medical UniversityDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical UniversityCollege of Public Health, Zhengzhou UniversityDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Oncology, Jingjiang People’s Hospital Affiliated With Yangzhou UniversityAbstract Cholesterol metabolism is abnormally active in tumour cells. Metabolic enzymes related to cholesterol metabolism are upregulated in tumours, but their nonmetabolic functions remain unclear. We found that MVK (mevalonate kinase) is upregulated in lung adenocarcinoma tissues vs. normal tissues and that its expression can be induced by constitutively activated Kras. By investigating the molecular mechanisms involved, we discovered that MVK interacts with TBK1, inhibiting TBK1 phosphorylation and thereby suppressing cGAS-Sting signalling. In addition, we found a negative correlation between MVK expression and CD8+ T-cell infiltration via a public database analysis. In summary, our study demonstrates the importance of the nonmetabolic function of MVK in modifying the immunological milieu and provides new targets for lung adenocarcinoma therapy.https://doi.org/10.1186/s40001-024-02186-8Mevalonate kinaseLung adenocarcinomaCGAS-Sting signallingKras |
| spellingShingle | Changsheng Zhou Jia Liu Xudong Hu Lu Lu Juan Hou Jian Wang Liqun Jiang Shuangshuang Huang Yu Lin Luyao Liu Lingling Cui Yiqian Liu Yufeng Huang MVK, induced by Kras, represses cGAS-Sting signalling in lung adenocarcinoma European Journal of Medical Research Mevalonate kinase Lung adenocarcinoma CGAS-Sting signalling Kras |
| title | MVK, induced by Kras, represses cGAS-Sting signalling in lung adenocarcinoma |
| title_full | MVK, induced by Kras, represses cGAS-Sting signalling in lung adenocarcinoma |
| title_fullStr | MVK, induced by Kras, represses cGAS-Sting signalling in lung adenocarcinoma |
| title_full_unstemmed | MVK, induced by Kras, represses cGAS-Sting signalling in lung adenocarcinoma |
| title_short | MVK, induced by Kras, represses cGAS-Sting signalling in lung adenocarcinoma |
| title_sort | mvk induced by kras represses cgas sting signalling in lung adenocarcinoma |
| topic | Mevalonate kinase Lung adenocarcinoma CGAS-Sting signalling Kras |
| url | https://doi.org/10.1186/s40001-024-02186-8 |
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