The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
HCAR1/MCT1 Regulates Tumor Ferroptosis through the Lactate-Mediated AMPK-SCD1 Activity and Its Therapeutic Implications
Open accessAbstract
Ferroptosis is a recently discovered form of programed cell death caused by the metabolically regulated lipid peroxidation and holds promise for cancer treatment, but its regulatory mechanisms remain elusive. In this study, we observe that lactate-rich liver cancer cells exhibit enhanced resistance to the ferroptotic damage induced by common ferroptosis inducers such as Ras-selective lethal small molecule 3 (RSL3) and Erastin and that the monocarboxylate transporter 1 (MCT1)-mediated lactate uptake could promote ATP production in hepatocellular carcinoma (HCC) cells and deactivate the energy sensor AMP-activated protein kinase (AMPK), leading to the upregulation of sterol regulatory element-binding protein 1 (SREBP1) and the downstream stearoyl-coenzyme A (CoA) desaturase-1 (SCD1) to enhance the production of anti-ferroptosis monounsaturated fatty acids. Additionally, blocking the lactate uptake via hydroxycarboxylic acid receptor 1 (HCAR1)/MCT1 inhibition promotes ferroptosis by activating the AMPK to downregulate SCD1, which may synergize with its acyl-coenzyme A synthetase 4 (ACSL4)-promoting effect to amplify the ferroptotic susceptibility. In vitro and in vivo evidence confirms that lactate regulates the ferroptosis of HCC cells and highlights its translational potential as a therapeutic target for ferroptosis-based tumor treatment.
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Cites
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ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition
Doll, S., Proneth, B., Tyurina, Y. Y., Panzilius, E., Kobayashi, S., Ingold, I., Irmler, M., Beckers, J., Aichler, M., Walch, A., et al. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2239 · Cited by 4,293
The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis
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Self-citationFSP1 is a glutathione-independent ferroptosis suppressor
Doll, S., Freitas, F. P., Shah, R., Aldrovandi, M., da Silva, M. C., Ingold, I., Goya Grocin, A., Xavier da Silva, T. N., Panzilius, E., Scheel, C. H., et al. (2019) · Nature · doi:10.1038/s41586-019-1707-0 · Cited by 3,341
CD8+ T cells regulate tumour ferroptosis during cancer immunotherapy
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Targeting Ferroptosis to Iron Out Cancer
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Cited by
The Cell Biology of Ferroptosis
Dixon, S. J., & Olzmann, J. A. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00703-5 · Cited by 1,596
Lactate metabolism in human health and disease
Li, X., Yang, Y., Zhang, B., Lin, X., Fu, X., An, Y., Zou, Y., Wang, J.-X., Wang, Z., & Yu, T. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01151-3 · Cited by 1,454
Ferroptosis in cancer and cancer immunotherapy
Zhao, L., Zhou, X., Xie, F., Zhang, L., Yan, H., Huang, J., Zhang, C., Zhou, F., Chen, J., & Zhang, L. (2022) · Cancer Communications · doi:10.1002/cac2.12250 · Cited by 684
Acyl-CoA synthase ACSL4: an essential target in ferroptosis and fatty acid metabolism
Ding, K., Liu, C., Li, L., Yang, M., Jiang, N., Luo, S., & Sun, L. (2023) · Chinese Medical Journal · doi:10.1097/cm9.0000000000002533 · Cited by 396
Huang, T., Zhou, M.-Y., Zou, G.-L., Hu, R.-H., Han, L., Zhang, Q.-X., & Zhao, X.-K. (2025) · Scientific Reports · doi:10.1038/s41598-025-88538-8 · Cited by 14
Metadata
- Authors
- Zhao, Y., Li, M., Yao, X., Fei, Y., Lin, Z., Li, Z., Cai, K., Zhao, Y., & Luo, Z.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2020-12
- Volume
- 33
- Issue
- 10
- Pages
- 108487
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W3112090163
- Cited by
- 412
- References
- 55
- FWCI
- 20.93
- Type
- journal article
- Language
- en
- Open access
- gold
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- Zhao, Y., Li, M., Yao, X., Fei, Y., Lin, Z., Li, Z., Cai, K., Zhao, Y., & Luo, Z. (2020). HCAR1/MCT1 Regulates Tumor Ferroptosis through the Lactate-Mediated AMPK-SCD1 Activity and Its Therapeutic Implications. Cell Reports. https://doi.org/10.1016/j.celrep.2020.108487
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