The DOI matches its Crossref record; 83 of the 83 references it cites were found in a registry or an index.
Tumors exploit FTO-mediated regulation of glycolytic metabolism to evade immune surveillance
Open accessAbstract
The ever-increasing understanding of the complexity of factors and regulatory layers that contribute to immune evasion facilitates the development of immunotherapies. However, the diversity of malignant tumors limits many known mechanisms in specific genetic and epigenetic contexts, manifesting the need to discover general driver genes. Here, we have identified the m6A demethylase FTO as an essential epitranscriptomic regulator utilized by tumors to escape immune surveillance through regulation of glycolytic metabolism. We show that FTO-mediated m6A demethylation in tumor cells elevates the transcription factors c-Jun, JunB, and C/EBPβ, which allows the rewiring of glycolytic metabolism. Fto knockdown impairs the glycolytic activity of tumor cells, which restores the function of CD8+ T cells, thereby inhibiting tumor growth. Furthermore, we developed a small-molecule compound, Dac51, that can inhibit the activity of FTO, block FTO-mediated immune evasion, and synergize with checkpoint blockade for better tumor control, suggesting reprogramming RNA epitranscriptome as a potential strategy for immunotherapy.
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Cited by
Xiong, J., He, J., Zhu, J., Pan, J., Liao, W., Ye, H., Wang, H., Song, Y., Du, Y., Cui, B., et al. (2022) · Molecular Cell · doi:10.1016/j.molcel.2022.02.033 · Cited by 804
FTO mediates LINE1 m 6 A demethylation and chromatin regulation in mESCs and mouse development
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Metadata
- Authors
- Liu, Y., Liang, G., Xu, H., Dong, W., Dong, Z., Qiu, Z., Zhang, Z., Li, F., Huang, Y., Li, Y., Wu, J., Yin, S., Zhang, Y., Guo, P., Liu, J., Xi, J. J., Jiang, P., Han, D., Yang, C.-G., & Xu, M. M.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2021-06
- Volume
- 33
- Issue
- 6
- Pages
- 1221-1233.e11
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W3158589775
- Cited by
- 361
- References
- 83
- FWCI
- 15.36
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Liu, Y., Liang, G., Xu, H., Dong, W., Dong, Z., Qiu, Z., Zhang, Z., Li, F., Huang, Y., Li, Y., Wu, J., Yin, S., Zhang, Y., Guo, P., Liu, J., Xi, J. J., Jiang, P., Han, D., Yang, C.-G., & Xu, M. M. (2021). Tumors exploit FTO-mediated regulation of glycolytic metabolism to evade immune surveillance. Cell Metabolism. https://doi.org/10.1016/j.cmet.2021.04.001
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