{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T20:09:00Z","timestamp":1789934940750,"version":"4.0.1"},"reference-count":44,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2027,1,1]],"date-time":"2027-01-01T00:00:00Z","timestamp":1798761600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2027,1,1]],"date-time":"2027-01-01T00:00:00Z","timestamp":1798761600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2027,1,1]],"date-time":"2027-01-01T00:00:00Z","timestamp":1798761600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2027,1,1]],"date-time":"2027-01-01T00:00:00Z","timestamp":1798761600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2027,1,1]],"date-time":"2027-01-01T00:00:00Z","timestamp":1798761600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2027,1,1]],"date-time":"2027-01-01T00:00:00Z","timestamp":1798761600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2027,1,1]],"date-time":"2027-01-01T00:00:00Z","timestamp":1798761600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100017683","name":"Dalian Science and Technology Innovation Fund","doi-asserted-by":"publisher","award":["2025JJ11PT004"],"award-info":[{"award-number":["2025JJ11PT004"]}],"id":[{"id":"10.13039\/501100017683","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cellular Signalling"],"published-print":{"date-parts":[[2027,1]]},"DOI":"10.1016\/j.cellsig.2026.112890","type":"journal-article","created":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T06:02:39Z","timestamp":1789279359000},"page":"112890","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Valproic acid inhibits glutamine uptake to induce ferroptosis in triple-negative breast cancer"],"prefix":"10.1016","volume":"149","author":[{"given":"Yisong","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiazhuo","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiting","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teng","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangping","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.cellsig.2026.112890_bb0005","first-page":"47","article-title":"Cancer incidence and mortality in China, 2022","volume":"4","author":"Han","year":"2024","journal-title":"J Natl Cancer Cent."},{"key":"10.1016\/j.cellsig.2026.112890_bb0010","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"10.1016\/j.cellsig.2026.112890_bb0015","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1002\/path.6475","article-title":"Sparking malignancy: nicotine as a driver of stemness and metastasis in triple-negative breast cancer","volume":"267","author":"Simpkins","year":"2025","journal-title":"J. Pathol."},{"key":"10.1016\/j.cellsig.2026.112890_bb0020","doi-asserted-by":"crossref","DOI":"10.1186\/s13046-025-03430-7","article-title":"Targeting glutamine metabolism as a potential target for cancer treatment","volume":"44","author":"Zou","year":"2025","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"10.1016\/j.cellsig.2026.112890_bb0025","doi-asserted-by":"crossref","DOI":"10.1016\/j.canlet.2025.217527","article-title":"Intranuclear TCA and mitochondrial overload: the nascent sprout of tumors metabolism","volume":"613","author":"Yuan","year":"2025","journal-title":"Cancer Lett."},{"key":"10.1016\/j.cellsig.2026.112890_bb0030","doi-asserted-by":"crossref","DOI":"10.1016\/j.molmet.2024.102037","article-title":"Identifying targetable metabolic dependencies across colorectal cancer progression","volume":"90","author":"Legge","year":"2024","journal-title":"Mol Metab."},{"issue":"24","key":"10.1016\/j.cellsig.2026.112890_bb0035","doi-asserted-by":"crossref","first-page":"6969","DOI":"10.1093\/emboj\/20.24.6969","article-title":"Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells","volume":"20","author":"G\u00f6ttlicher","year":"2001","journal-title":"EMBO J."},{"key":"10.1016\/j.cellsig.2026.112890_bb0040","doi-asserted-by":"crossref","DOI":"10.1038\/s41419-023-06049-8","article-title":"M5C-methylated lncRNA NR_033928 promotes gastric cancer proliferation by stabilizing GLS mRNA to promote glutamine metabolism reprogramming","volume":"14","author":"Fang","year":"2023","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.cellsig.2026.112890_bb0045","doi-asserted-by":"crossref","DOI":"10.3390\/antiox12030683","article-title":"Glutamine starvation affects cell cycle, oxidative homeostasis and metabolism in colorectal cancer cells","volume":"12","author":"Spada","year":"2023","journal-title":"Antioxidants"},{"key":"10.1016\/j.cellsig.2026.112890_bb0050","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.ccr.2013.08.020","article-title":"Glutamine sensitivity analysis identifies the xCT antiporter as a common triple-negative breast tumor therapeutic target","volume":"24","author":"Timmerman","year":"2013","journal-title":"Cancer Cell"},{"key":"10.1016\/j.cellsig.2026.112890_bb0055","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1158\/1535-7163.MCT-13-0870","article-title":"Antitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer","volume":"13","author":"Gross","year":"2014","journal-title":"Mol. Cancer Ther."},{"key":"10.1016\/j.cellsig.2026.112890_bb0060","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1002229","article-title":"Glutamine synthetase is a genetic determinant of cell type-specific glutamine independence in breast epithelia","volume":"7","author":"Kung","year":"2011","journal-title":"PLoS Genet."},{"key":"10.1016\/j.cellsig.2026.112890_bb0065","doi-asserted-by":"crossref","DOI":"10.3390\/antiox13060745","article-title":"GLS and GLS2 glutaminase isoenzymes in the antioxidant system of cancer cells","volume":"13","author":"De Los Santos-Jim\u00e9nez","year":"2024","journal-title":"Antioxidants"},{"key":"10.1016\/j.cellsig.2026.112890_bb0070","article-title":"Iron and ferroptosis in kidney disease: molecular and metabolic mechanisms","volume":"16","author":"Wang","year":"2025","journal-title":"Front. Immunol."},{"key":"10.1016\/j.cellsig.2026.112890_bb0075","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/s41580-020-00324-8","article-title":"Ferroptosis: mechanisms, biology and role in disease","volume":"22","author":"Jiang","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.cellsig.2026.112890_bb0080","doi-asserted-by":"crossref","DOI":"10.1111\/cpr.70036","article-title":"Glutaminase-1 mediated glutaminolysis to glutathione synthesis maintains redox homeostasis and modulates ferroptosis sensitivity in cancer cells","author":"Bai","year":"2025","journal-title":"Cell Prolif."},{"key":"10.1016\/j.cellsig.2026.112890_bb0085","article-title":"Emerging roles of energy metabolism in ferroptosis regulation of tumor cells","volume":"1875","author":"Yao","year":"2021","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"10.1016\/j.cellsig.2026.112890_bb0090","doi-asserted-by":"crossref","first-page":"29","DOI":"10.37796\/2211-8039.1445","article-title":"Glutaminase \u2014 a potential target for cancer treatment","volume":"14","author":"Anthony","year":"2024","journal-title":"Biomedicine"},{"key":"10.1016\/j.cellsig.2026.112890_bb0095","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1158\/1535-7163.MCT-23-0041","article-title":"A carbonic anhydrase IX\/SLC1A5 Axis regulates glutamine metabolism dependent ferroptosis in hypoxic tumor cells","volume":"22","author":"Venkateswaran","year":"2023","journal-title":"Mol. Cancer Ther."},{"key":"10.1016\/j.cellsig.2026.112890_bb0100","first-page":"40","article-title":"Transition of psychotropic drugs in Japanese pharmacopoeia (JP) (part 17)","volume":"51","author":"Yanagisawa","year":"2016","journal-title":"Yakushigaku Zasshi"},{"key":"10.1016\/j.cellsig.2026.112890_bb0105","doi-asserted-by":"crossref","unstructured":"Z. Tolou-Ghamari, A. A. Palizban. Review of sodium valproate clinical and biochemical properties. Zahedan J. Res. Med. Sci. 17(8):e2207. 10.17795\/zjrms-2207.","DOI":"10.17795\/zjrms-2207"},{"key":"10.1016\/j.cellsig.2026.112890_bb0110","doi-asserted-by":"crossref","DOI":"10.1177\/09636897211027524","article-title":"Valproic acid suppresses breast cancer cell growth through triggering pyruvate kinase M2 isoform mediated Warburg effect","volume":"30","author":"Li","year":"2021","journal-title":"Cell Transplant."},{"key":"10.1016\/j.cellsig.2026.112890_bb0115","doi-asserted-by":"crossref","DOI":"10.3390\/jcm14082673","article-title":"Repurposing antiepileptic drugs for cancer: a promising therapeutic strategy","volume":"14","author":"Tarawneh","year":"2025","journal-title":"J. Clin. Med."},{"key":"10.1016\/j.cellsig.2026.112890_bb0120","article-title":"Valproic acid targets IDH1 mutants through alteration of lipid metabolism","volume":"2","author":"Elahi","year":"2024","journal-title":"NPJ Metab. Health Dis."},{"key":"10.1016\/j.cellsig.2026.112890_bb0125","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1093\/abbs\/gmab002","article-title":"Inhibition of lipogenesis and induction of apoptosis by valproic acid in prostate cancer cells via the C\/EBP\u03b1\/SREBP-1 pathway","volume":"53","author":"Pang","year":"2021","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"10.1016\/j.cellsig.2026.112890_bb0130","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1002\/9780470942390.mo100161","article-title":"Ethical considerations in mouse experiments","volume":"1","author":"Baertschi","year":"2011","journal-title":"Curr. Protoc. Mouse Biol."},{"key":"10.1016\/j.cellsig.2026.112890_bb0135","doi-asserted-by":"crossref","DOI":"10.1002\/advs.202100997","article-title":"Emerging roles of energy metabolism in ferroptosis regulation of tumor cells","volume":"8","author":"Yao","year":"2021","journal-title":"Adv. Sci."},{"key":"10.1016\/j.cellsig.2026.112890_bb0140","doi-asserted-by":"crossref","first-page":"D1670","DOI":"10.1093\/nar\/gkae973","article-title":"Generic diagramming platform (GDP): a comprehensive database of high-quality biomedical graphics","volume":"53","author":"Jiang","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.cellsig.2026.112890_bb0145","first-page":"44","article-title":"Metabolic reprogramming in triple-negative breast cancer, Cancer","volume":"17","author":"Wang","year":"2020","journal-title":"Biol. Med."},{"key":"10.1016\/j.cellsig.2026.112890_bb0150","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1186\/1471-2407-14-941","article-title":"Metabolic characterization of triple negative breast cancer","volume":"14","author":"Cao","year":"2014","journal-title":"BMC Cancer"},{"key":"10.1016\/j.cellsig.2026.112890_bb0155","doi-asserted-by":"crossref","DOI":"10.3390\/metabo16010060","article-title":"Mitochondrial redox vulnerabilities in triple-negative breast cancer: integrative perspectives and emerging therapeutic strategies","volume":"16","author":"Cruz-Gregorio","year":"2026","journal-title":"Metabolites"},{"key":"10.1016\/j.cellsig.2026.112890_bb0160","article-title":"Real-time tracking of ASCT2-mediated glutamine uptake in living tumors with a bioorthogonal bioluminescent probe","volume":"12","author":"Zhou","year":"2025","journal-title":"Adv. Sci."},{"key":"10.1016\/j.cellsig.2026.112890_bb0165","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/nm.4464","article-title":"Pharmacological blockade of ASCT2-dependent glutamine transport leads to antitumor efficacy in preclinical models","volume":"24","author":"Schulte","year":"2018","journal-title":"Nat. Med."},{"key":"10.1016\/j.cellsig.2026.112890_bb0170","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1021\/acs.jmedchem.3c01093","article-title":"Discovery of novel aminobutanoic acid-based ASCT2 inhibitors for the treatment of non-small-cell lung cancer","volume":"67","author":"Qin","year":"2024","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.cellsig.2026.112890_bb0175","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1007\/s00726-017-2436-z","article-title":"GPNA inhibits the sodium-independent transport system L for neutral amino acids","volume":"49","author":"Chiu","year":"2017","journal-title":"Amino Acids"},{"key":"10.1016\/j.cellsig.2026.112890_bb0180","doi-asserted-by":"crossref","first-page":"785","DOI":"10.3389\/fphar.2018.00785","article-title":"Disruption of amino acid homeostasis by novel ASCT2 inhibitors involves multiple targets","volume":"9","author":"Br\u00f6er","year":"2018","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.cellsig.2026.112890_bb0185","series-title":"Identification of ASCT2 as the Primary Serine Transporter in Cancer","author":"Conger","year":"2024"},{"key":"10.1016\/j.cellsig.2026.112890_bb0190","article-title":"Clinical application prospects of traditional Chinese medicine as adjuvant therapy for metabolic reprogramming in colorectal cancer","volume":"16","author":"Liu","year":"2025","journal-title":"Front. Immunol."},{"key":"10.1016\/j.cellsig.2026.112890_bb0195","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1158\/1078-0432.CCR-12-2334","article-title":"SLC1A5 mediates glutamine transport required for lung cancer cell growth and survival","volume":"19","author":"Hassanein","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.cellsig.2026.112890_bb0200","doi-asserted-by":"crossref","unstructured":"A. Br\u00f6er, C. Wagner, F. Lang, et al., Neutral amino acid transporter ASCT2 displays substrate-induced Na+ exchange and a substrate-gated anion conductance, Biochem. J. 346 Pt 3 (2000) 705\u2013710.","DOI":"10.1042\/bj3460705"},{"key":"10.1016\/j.cellsig.2026.112890_bb0205","doi-asserted-by":"crossref","first-page":"2877","DOI":"10.1074\/jbc.RA117.001342","article-title":"The glutamine transporter ASCT2 (SLC1A5) promotes tumor growth independently of the amino acid transporter LAT1 (SLC7A5)","volume":"293","author":"Cormerais","year":"2018","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.cellsig.2026.112890_bb0210","doi-asserted-by":"crossref","DOI":"10.1074\/jbc.M115.700534","article-title":"Deletion of amino acid transporter ASCT2 (SLC1A5) reveals an essential role for transporters SNAT1 (SLC38A1) and SNAT2 (SLC38A2) to sustain glutaminolysis in cancer cells","volume":"291","author":"Br\u00f6er","year":"2016","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.cellsig.2026.112890_bb0215","article-title":"Valproic acid induces ferroptosis and suppresses the proliferation of MDA-MB-231 cells by targeting FDFT1","volume":"16","author":"Zhang","year":"2025","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.cellsig.2026.112890_bb0220","doi-asserted-by":"crossref","DOI":"10.1038\/onc.2015.381","article-title":"ASCT2\/SLC1A5 controls glutamine uptake and tumour growth in triple-negative basal-like breast cancer","volume":"35","author":"van Geldermalsen","year":"2016","journal-title":"Oncogene"}],"container-title":["Cellular Signalling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0898656826005498?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0898656826005498?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T19:46:38Z","timestamp":1789933598000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0898656826005498"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2027,1]]},"references-count":44,"alternative-id":["S0898656826005498"],"URL":"https:\/\/doi.org\/10.1016\/j.cellsig.2026.112890","relation":{},"ISSN":["0898-6568"],"issn-type":[{"value":"0898-6568","type":"print"}],"subject":[],"published":{"date-parts":[[2027,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Valproic acid inhibits glutamine uptake to induce ferroptosis in triple-negative breast cancer","name":"articletitle","label":"Article Title"},{"value":"Cellular Signalling","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.cellsig.2026.112890","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"112890"}}