Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/146149
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dc.contributor.authorZhao, Youboen_US
dc.contributor.authorLi, Menghuanen_US
dc.contributor.authorYao, Xuemeien_US
dc.contributor.authorFei, Yangen_US
dc.contributor.authorLin, Zhenghongen_US
dc.contributor.authorLi, Zhengguoen_US
dc.contributor.authorCai, Kaiyongen_US
dc.contributor.authorZhao, Yanlien_US
dc.contributor.authorLuo, Zhongen_US
dc.date.accessioned2021-01-28T04:17:46Z-
dc.date.available2021-01-28T04:17:46Z-
dc.date.issued2020-
dc.identifier.citationZhao, 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, 33(10). https://dx.doi.org/10.1016/j.celrep.2020.108487en_US
dc.identifier.issn2211-1247en_US
dc.identifier.other0000-0002-9019-3314-
dc.identifier.urihttps://hdl.handle.net/10356/146149-
dc.description.abstractFerroptosis 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.en_US
dc.language.isoenen_US
dc.relation.ispartofCell reportsen_US
dc.rights© 2020 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).en_US
dc.subjectScience::Chemistryen_US
dc.titleHCAR1/MCT1 regulates tumor ferroptosis through the lactate-mediated AMPK-SCD1 activity and its therapeutic implicationsen_US
dc.typeJournal Articleen
dc.contributor.schoolSchool of Physical and Mathematical Sciencesen_US
dc.identifier.doi10.1016/j.celrep.2020.108487-
dc.description.versionPublished versionen_US
dc.identifier.pmid33296645-
dc.identifier.scopus2-s2.0-85097481152-
dc.identifier.issue10en_US
dc.identifier.volume33en_US
dc.subject.keywordsLactateen_US
dc.subject.keywordsFerroptosisen_US
item.fulltextWith Fulltext-
item.grantfulltextopen-
crisitem.author.deptSchool of Chemistry, Chemical Engineering and Biotechnology-
Appears in Collections:SPMS Journal Articles
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