MVK, induced by Kras, represses cGAS-Sting signalling in lung adenocarcinoma
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<sup>+</sup> 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.
Authors
- Xudong Hu (ORCID: https://orcid.org/0000-0002-4297-8360)
- Yu‐Lung Lin (ORCID: https://orcid.org/0000-0001-5437-9958)
- Juan Hou (ORCID: https://orcid.org/0000-0003-3869-2658)
- Lingling Cui (ORCID: https://orcid.org/0000-0003-1367-5851)
- Liqun Jiang (ORCID: https://orcid.org/0000-0002-8541-7539)
- Yiqian Liu
- Shuangshuang Huang
- Lu Lu (ORCID: https://orcid.org/0000-0002-2255-0391)
- Jian Wang (ORCID: https://orcid.org/0000-0003-2291-640X)
- Jia Liu (ORCID: https://orcid.org/0000-0002-8474-1185)
- Yu‐Feng Huang (ORCID: https://orcid.org/0000-0002-8305-6776)
- Changsheng Zhou (ORCID: https://orcid.org/0000-0002-4297-364X)
- Lei Liu (ORCID: https://orcid.org/0000-0002-4604-4629)
Institutions
- Shanghai Jiao Tong University (CN)
- Wenzhou Medical University (CN)
- Shanghai Chest Hospital (CN)
- Zhengzhou University (CN)
- Suzhou Municipal Hospital (CN)
- Jiangsu Province Hospital (CN)
- First People's Hospital of Jingzhou (CN)
- Yangzhou University (CN)
- Nanjing Medical University (CN)
Publication Details
- Journal
- European journal of medical research
- Published
- 2025-01-22
- DOI
- https://doi.org/10.1186/s40001-024-02186-8
- Primary Topic
- interferon and immune responses
- Type
- article
- Field-Weighted Citation Impact
- 0.00