OASL enhances mRNA translation and reprograms lipid metabolism to promote cancer progression
Type I interferons (IFN-Is) are central coordinators of tumor-immune system interactions. Accumulating evidence suggests that persistent IFN-Is and a subset of IFN-stimulated genes (ISGs) might promote tumor development, but the regulation of mRNA translation and lipid metabolism during this process remains unknown. Here, we report that oligoadenylate synthetase-like (OASL) is a key ISG in mediating the pro-tumor effects of IFN-Is. OASL is highly expressed in human cancers and is associated with poor prognosis. We identify physical and functional interactions between OASL and ribosome. OASL enhances global translation initiation with the preference for a subset of mRNAs involved in fatty acid (FA) synthesis by interaction with ribosomes. Using both loss- and gain-of-function studies, we find that OASL reprograms FA metabolism to enhance oncogenesis, which can be inhibited by an FA synthesis inhibitor. Our results define OASL as an important factor in regulating mRNA translation, mediating tumor-promoting functions of IFN-Is, and providing potential therapeutic interventions.
Authors
- Yuchun Li (ORCID: https://orcid.org/0000-0001-5508-4721)
- Erwei Song (ORCID: https://orcid.org/0000-0002-5400-9049)
- Fei Han (ORCID: https://orcid.org/0000-0001-5363-7556)
- Hai‐Qiang Mai (ORCID: https://orcid.org/0000-0002-9035-6814)
- Li Yuan (ORCID: https://orcid.org/0000-0001-5602-6910)
- Qian Zhong (ORCID: https://orcid.org/0000-0003-1071-6996)
- Shi-Bing Li
- Lin‐Quan Tang (ORCID: https://orcid.org/0000-0002-9613-7305)
- H. Zhang (ORCID: https://orcid.org/0000-0002-0687-2286)
- Li Sun (ORCID: https://orcid.org/0000-0001-5902-6684)
- Mu‐Sheng Zeng (ORCID: https://orcid.org/0000-0003-3509-5591)
- Lawrence S. Young (ORCID: https://orcid.org/0000-0003-3919-4298)
- Minghui Gao
- Gong Zhang (ORCID: https://orcid.org/0000-0003-0418-3433)
- Qing‐Yu He (ORCID: https://orcid.org/0000-0003-0503-9492)
- Yuantao Liu
- Qianying Zhu (ORCID: https://orcid.org/0000-0003-3085-5467)
- Zhi-Rui Lin
Institutions
- Sun Yat-sen University (CN)
- Jinan University (CN)
- Chinese Academy of Sciences (CN)
- Guangzhou Institutes of Biomedicine and Health (CN)
- University of Warwick (GB)
- Sixth Affiliated Hospital of Sun Yat-sen University (CN)
- Sun Yat-sen Memorial Hospital (CN)
- Sun Yat-sen University Cancer Center (CN)
- State Key Laboratory of Oncology in South China
Publication Details
- Journal
- Cell Reports
- Published
- 2025-07-01
- DOI
- https://doi.org/10.1016/j.celrep.2025.115901
- Citations
- 8
- Primary Topic
- Cancer, Lipids, and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 7.49
Funders
- Guangdong Innovative and Entrepreneurial Research Team Program
- National Natural Science Foundation of China
- Sun Yat-sen University
- Guangdong Science and Technology Department
- National Key Research and Development Program of China
- Sun Yat-sen University Cancer Center