{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:47:46Z","timestamp":1792784866540,"version":"4.5.0"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T00:00:00Z","timestamp":1718150400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T00:00:00Z","timestamp":1718150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070676"],"award-info":[{"award-number":["82070676"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82373265"],"award-info":[{"award-number":["82373265"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31930020"],"award-info":[{"award-number":["31930020"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82103430"],"award-info":[{"award-number":["82103430"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Health Commission medical health science and technology development research project"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive cancer characterized by a poor prognosis and resistance to chemotherapy. In this study, utilizing scRNA-seq, we discovered that the tetra-transmembrane protein mal, T cell differentiation protein 2 (MAL2), exhibited specific enrichment in ICC cancer cells and was strongly associated with a poor prognosis. The inhibition of MAL2 effectively suppressed cell proliferation, invasion, and migration. Transcriptomics and metabolomics analyses suggested that MAL2 promoted lipid accumulation in ICC by stabilizing EGFR membrane localization and activated the PI3K\/AKT\/SREBP-1 axis. Molecular docking and Co-IP proved that MAL2 interacted directly with EGFR. Based on constructed ICC organoids, the downregulation of MAL2 enhanced apoptosis and sensitized ICC cells to cisplatin. Lastly, we conducted a virtual screen to identify sarizotan, a small molecule inhibitor of MAL2, and successfully validated its ability to inhibit MAL2 function. Our findings highlight the tumorigenic role of MAL2 and its involvement in cisplatin sensitivity, suggesting the potential for novel combination therapeutic strategies in ICC.<\/jats:p>","DOI":"10.1038\/s41419-024-06775-7","type":"journal-article","created":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T08:02:38Z","timestamp":1718179358000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["MAL2 reprograms lipid metabolism in intrahepatic cholangiocarcinoma via EGFR\/SREBP-1 pathway based on single-cell RNA sequencing"],"prefix":"10.1038","volume":"15","author":[{"given":"Tian","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hengsong","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohu","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shipeng","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuliang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5849-0098","authenticated-orcid":false,"given":"Xuehao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8516-819X","authenticated-orcid":false,"given":"Weiwei","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6589-797X","authenticated-orcid":false,"given":"Yongxiang","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,12]]},"reference":[{"key":"6775_CR1","doi-asserted-by":"publisher","first-page":"198","DOI":"10.3322\/caac.21759","volume":"73","author":"D Moris","year":"2023","unstructured":"Moris D, Palta M, Kim C, Allen PJ, Morse MA, Lidsky ME. Advances in the treatment of intrahepatic cholangiocarcinoma: an overview of the current and future therapeutic landscape for clinicians. CA Cancer J Clin. 2023;73:198\u2013222.","journal-title":"CA Cancer J Clin"},{"key":"6775_CR2","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.1002\/hep.30289","volume":"69","author":"AE Sirica","year":"2019","unstructured":"Sirica AE, Gores GJ, Groopman JD, Selaru FM, Strazzabosco M, Wei Wang X, et al. Intrahepatic cholangiocarcinoma: continuing challenges and translational advances. Hepatology. 2019;69:1803\u201315.","journal-title":"Hepatology"},{"key":"6775_CR3","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1016\/j.jhep.2019.10.009","volume":"72","author":"RK Kelley","year":"2020","unstructured":"Kelley RK, Bridgewater J, Gores GJ, Zhu AX. Systemic therapies for intrahepatic cholangiocarcinoma. J Hepatol. 2020;72:353\u201363.","journal-title":"J Hepatol"},{"key":"6775_CR4","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1038\/nri.2017.76","volume":"18","author":"E Papalexi","year":"2018","unstructured":"Papalexi E, Satija R. Single-cell RNA sequencing to explore immune cell heterogeneity. Nat Rev Immunol. 2018;18:35\u201345.","journal-title":"Nat Rev Immunol"},{"key":"6775_CR5","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.694","volume":"12","author":"D Jovic","year":"2022","unstructured":"Jovic D, Liang X, Zeng H, Lin L, Xu F, Luo Y. Single-cell RNA sequencing technologies and applications: a brief overview. Clin Transl Med. 2022;12:e694.","journal-title":"Clin Transl Med"},{"key":"6775_CR6","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1083\/jcb.200206033","volume":"159","author":"MC de Marco","year":"2002","unstructured":"de Marco MC, Mart\u00edn-Belmonte F, Kremer L, Albar JP, Correas I, Vaerman JP, et al. MAL2, a novel raft protein of the MAL family, is an essential component of the machinery for transcytosis in hepatoma HepG2 cells. J Cell Biol. 2002;159:37\u201344.","journal-title":"J Cell Biol"},{"key":"6775_CR7","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1042\/BJ20140468","volume":"463","author":"JG In","year":"2014","unstructured":"In JG, Striz AC, Bernad A, Tuma PL. Serine\/threonine kinase 16 and MAL2 regulate constitutive secretion of soluble cargo in hepatic cells. Biochem J. 2014;463:201\u201313.","journal-title":"Biochem J"},{"key":"6775_CR8","doi-asserted-by":"publisher","first-page":"e140837","DOI":"10.1172\/JCI140837","volume":"131","author":"Y Fang","year":"2021","unstructured":"Fang Y, Wang L, Wan C, Sun Y, Van der Jeught K, Zhou Z, et al. MAL2 drives immune evasion in breast cancer by suppressing tumor antigen presentation. J Clin Investig. 2021;131:e140837.","journal-title":"J Clin Investig"},{"key":"6775_CR9","doi-asserted-by":"publisher","first-page":"422","DOI":"10.3390\/cancers12020422","volume":"12","author":"A L\u00f3pez-Coral","year":"2020","unstructured":"L\u00f3pez-Coral A, Del Vecchio GJ, Chahine JJ, Kallakury BV, Tuma PL. MAL2-induced actin-based protrusion formation is anti-oncogenic in hepatocellular carcinoma. Cancers. 2020;12:422.","journal-title":"Cancers"},{"key":"6775_CR10","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1016\/j.surg.2013.03.010","volume":"154","author":"D Eguchi","year":"2013","unstructured":"Eguchi D, Ohuchida K, Kozono S, Ikenaga N, Shindo K, Cui L, et al. MAL2 expression predicts distant metastasis and short survival in pancreatic cancer. Surgery. 2013;154:573\u201382.","journal-title":"Surgery"},{"key":"6775_CR11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2022.100479","volume":"4","author":"B Paul","year":"2022","unstructured":"Paul B, Lewinska M, Andersen JB. Lipid alterations in chronic liver disease and liver cancer. JHEP Rep. 2022;4:100479.","journal-title":"JHEP Rep"},{"key":"6775_CR12","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1002\/mc.20094","volume":"45","author":"W Loilome","year":"2006","unstructured":"Loilome W, Yongvanit P, Wongkham C, Tepsiri N, Sripa B, Sithithaworn P, et al. Altered gene expression in Opisthorchis viverrini-associated cholangiocarcinoma in hamster model. Mol Carcinog. 2006;45:279\u201387.","journal-title":"Mol Carcinog"},{"key":"6775_CR13","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.696961","volume":"12","author":"J Tomacha","year":"2021","unstructured":"Tomacha J, Dokduang H, Padthaisong S, Namwat N, Klanrit P, Phetcharaburanin J, et al. Targeting fatty acid synthase modulates metabolic pathways and inhibits cholangiocarcinoma cell progression. Front Pharmacol. 2021;12:696961.","journal-title":"Front Pharmacol"},{"key":"6775_CR14","doi-asserted-by":"publisher","first-page":"1617","DOI":"10.1002\/hep.32344","volume":"76","author":"M Ruiz de Gauna","year":"2022","unstructured":"Ruiz de Gauna M, Biancaniello F, Gonz\u00e1lez-Romero F, Rodrigues PM, Lapitz A, G\u00f3mez-Santos B, et al. Cholangiocarcinoma progression depends on the uptake and metabolization of extracellular lipids. Hepatology. 2022;76:1617\u201333.","journal-title":"Hepatology"},{"key":"6775_CR15","doi-asserted-by":"publisher","first-page":"3006","DOI":"10.1172\/JCI127201","volume":"129","author":"Y Cao","year":"2019","unstructured":"Cao Y. Adipocyte and lipid metabolism in cancer drug resistance. J Clin Investig. 2019;129:3006\u201317.","journal-title":"J Clin Investig"},{"key":"6775_CR16","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32101-w","volume":"13","author":"Y Tan","year":"2022","unstructured":"Tan Y, Li J, Zhao G, Huang KC, Cardenas H, Wang Y, et al. Metabolic reprogramming from glycolysis to fatty acid uptake and beta-oxidation in platinum-resistant cancer cells. Nat Commun. 2022;13:4554.","journal-title":"Nat Commun"},{"key":"6775_CR17","doi-asserted-by":"publisher","first-page":"333","DOI":"10.3322\/caac.21670","volume":"71","author":"DR Schmidt","year":"2021","unstructured":"Schmidt DR, Patel R, Kirsch DG, Lewis CA, Vander Heiden MG, Locasale JW. Metabolomics in cancer research and emerging applications in clinical oncology. CA Cancer J Clin. 2021;71:333\u201358.","journal-title":"CA Cancer J Clin"},{"key":"6775_CR18","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/s40880-018-0301-4","volume":"38","author":"C Cheng","year":"2018","unstructured":"Cheng C, Geng F, Cheng X, Guo D. Lipid metabolism reprogramming and its potential targets in cancer. Cancer Commun. 2018;38:27.","journal-title":"Cancer Commun"},{"key":"6775_CR19","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1007\/112_2020_51","volume":"185","author":"T Petan","year":"2023","unstructured":"Petan T. Lipid droplets in cancer. Rev Physiol Biochem Pharmacol. 2023;185:53\u201386.","journal-title":"Rev Physiol Biochem Pharmacol"},{"key":"6775_CR20","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1038\/nrendo.2017.91","volume":"13","author":"H Shimano","year":"2017","unstructured":"Shimano H, Sato R. SREBP-regulated lipid metabolism: convergent physiology \u2013 divergent pathophysiology. Nat Rev Endocrinol. 2017;13:710\u201330.","journal-title":"Nat Rev Endocrinol"},{"key":"6775_CR21","doi-asserted-by":"publisher","first-page":"31189","DOI":"10.1073\/pnas.2017152117","volume":"117","author":"J Yi","year":"2020","unstructured":"Yi J, Zhu J, Wu J, Thompson CB, Jiang X. Oncogenic activation of PI3K-AKT-mTOR signaling suppresses ferroptosis via SREBP-mediated lipogenesis. Proc Natl Acad Sci USA. 2020;117:31189\u201397.","journal-title":"Proc Natl Acad Sci USA"},{"key":"6775_CR22","doi-asserted-by":"publisher","first-page":"2619","DOI":"10.2174\/13816128113199990486","volume":"20","author":"D Guo","year":"2014","unstructured":"Guo D, Bell EH, Mischel P, Chakravarti A. Targeting SREBP-1-driven lipid metabolism to treat cancer. Curr Pharm Des. 2014;20:2619\u201326.","journal-title":"Curr Pharm Des"},{"key":"6775_CR23","doi-asserted-by":"publisher","first-page":"2547","DOI":"10.1007\/s00018-019-03092-7","volume":"76","author":"S Fatima","year":"2019","unstructured":"Fatima S, Hu X, Gong RH, Huang C, Chen M, Wong HLX, et al. Palmitic acid is an intracellular signaling molecule involved in disease development. Cell Mol Life Sci. 2019;76:2547\u201357.","journal-title":"Cell Mol Life Sci"},{"key":"6775_CR24","doi-asserted-by":"publisher","first-page":"e46666","DOI":"10.15252\/embr.201846666","volume":"19","author":"PJ Ko","year":"2018","unstructured":"Ko PJ, Dixon SJ. Protein palmitoylation and cancer. EMBO Rep. 2018;19:e46666.","journal-title":"EMBO Rep"},{"key":"6775_CR25","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1038\/s41421-022-00515-x","volume":"9","author":"Q Zhang","year":"2023","unstructured":"Zhang Q, Yang X, Wu J, Ye S, Gong J, Cheng WM, et al. Reprogramming of palmitic acid induced by dephosphorylation of ACOX1 promotes \u03b2-catenin palmitoylation to drive colorectal cancer progression. Cell Discov. 2023;9:26.","journal-title":"Cell Discov"},{"key":"6775_CR26","doi-asserted-by":"publisher","first-page":"4861","DOI":"10.1038\/onc.2012.617","volume":"32","author":"D Sia","year":"2013","unstructured":"Sia D, Tovar V, Moeini A, Llovet JM. Intrahepatic cholangiocarcinoma: pathogenesis and rationale for molecular therapies. Oncogene. 2013;32:4861\u201370.","journal-title":"Oncogene"},{"key":"6775_CR27","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.110160","volume":"37","author":"J Jeong","year":"2021","unstructured":"Jeong J, Shin JH, Li W, Hong JY, Lim J, Hwang JY, et al. MAL2 mediates the formation of stable HER2 signaling complexes within lipid raft-rich membrane protrusions in breast cancer cells. Cell Rep. 2021;37:110160.","journal-title":"Cell Rep"},{"key":"6775_CR28","doi-asserted-by":"publisher","first-page":"2255","DOI":"10.3390\/jcm9072255","volume":"9","author":"W Jin","year":"2020","unstructured":"Jin W. ErBb family proteins in cholangiocarcinoma and clinical implications. J Clin Med. 2020;9:2255.","journal-title":"J Clin Med"},{"key":"6775_CR29","doi-asserted-by":"publisher","first-page":"a017020","DOI":"10.1101\/cshperspect.a017020","volume":"6","author":"C B\u00f6kel","year":"2014","unstructured":"B\u00f6kel C, Brand M. Endocytosis and signaling during development. Cold Spring Harb Perspect Biol. 2014;6:a017020.","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"6775_CR30","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1002\/1878-0261.12155","volume":"12","author":"S Sigismund","year":"2018","unstructured":"Sigismund S, Avanzato D, Lanzetti L. Emerging functions of the EGFR in cancer. Mol Oncol. 2018;12:3\u201320.","journal-title":"Mol Oncol"},{"key":"6775_CR31","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.bbrc.2021.02.146","volume":"554","author":"B Zhang","year":"2021","unstructured":"Zhang B, Xiao J, Cheng X, Liu T. MAL2 interacts with IQGAP1 to promote pancreatic cancer progression by increasing ERK1\/2 phosphorylation. Biochem Biophys Res Commun. 2021;554:63\u201370.","journal-title":"Biochem Biophys Res Commun"},{"key":"6775_CR32","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1016\/j.bbrc.2018.08.187","volume":"504","author":"A Bhandari","year":"2018","unstructured":"Bhandari A, Shen Y, Sindan N, Xia E, Gautam B, Lv S, et al. MAL2 promotes proliferation, migration, and invasion through regulating epithelial-mesenchymal transition in breast cancer cell lines. Biochem Biophys Res Commun. 2018;504:434\u20139.","journal-title":"Biochem Biophys Res Commun"},{"key":"6775_CR33","doi-asserted-by":"publisher","first-page":"e20201606","DOI":"10.1084\/jem.20201606","volume":"218","author":"X Bian","year":"2021","unstructured":"Bian X, Liu R, Meng Y, Xing D, Xu D, Lu Z. Lipid metabolism and cancer. J Exp Med. 2021;218:e20201606.","journal-title":"J Exp Med"},{"key":"6775_CR34","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1002\/hep.30319","volume":"70","author":"JM Banales","year":"2019","unstructured":"Banales JM, I\u00f1arrairaegui M, Arbelaiz A, Milkiewicz P, Muntan\u00e9 J, Mu\u00f1oz-Bellvis L, et al. Serum metabolites as diagnostic biomarkers for cholangiocarcinoma, hepatocellular carcinoma, and primary sclerosing cholangitis. Hepatology. 2019;70:547\u201362.","journal-title":"Hepatology"},{"key":"6775_CR35","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1016\/j.it.2023.06.001","volume":"44","author":"Y Wang","year":"2023","unstructured":"Wang Y, Huang T, Gu J, Lu L. Targeting the metabolism of tumor-infiltrating regulatory T cells. Trends Immunol. 2023;44:598\u2013612.","journal-title":"Trends Immunol"},{"key":"6775_CR36","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.3389\/fonc.2020.01025","volume":"10","author":"B Zhang","year":"2020","unstructured":"Zhang B, Zhou BH, Xiao M, Li H, Guo L, Wang MX, et al. KDM5C represses FASN-mediated lipid metabolism to exert tumor suppressor activity in intrahepatic cholangiocarcinoma. Front Oncol. 2020;10:1025.","journal-title":"Front Oncol"},{"key":"6775_CR37","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/s41419-022-05540-y","volume":"14","author":"X Yu","year":"2023","unstructured":"Yu X, Tong H, Chen J, Tang C, Wang S, Si Y, et al. CircRNA MBOAT2 promotes intrahepatic cholangiocarcinoma progression and lipid metabolism reprogramming by stabilizing PTBP1 to facilitate FASN mRNA cytoplasmic export. Cell Death Dis 2023;14:20.","journal-title":"Cell Death Dis"},{"key":"6775_CR38","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1186\/s13046-023-02842-7","volume":"42","author":"Y Chen","year":"2023","unstructured":"Chen Y, Xu X, Wang Y, Zhang Y, Zhou T, Jiang W, et al. Hypoxia-induced SKA3 promoted cholangiocarcinoma progression and chemoresistance by enhancing fatty acid synthesis via the regulation of PAR-dependent HIF-1a deubiquitylation. J Exp Clin Cancer Res. 2023;42:265.","journal-title":"J Exp Clin Cancer Res"},{"key":"6775_CR39","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2020.104466","volume":"115","author":"J Ma","year":"2020","unstructured":"Ma J, Feng J, Zhou X. Long non-coding RNA HAGLROS regulates lipid metabolism reprogramming in intrahepatic cholangiocarcinoma via the mTOR signaling pathway. Exp Mol Pathol. 2020;115:104466.","journal-title":"Exp Mol Pathol"},{"key":"6775_CR40","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.1600200","volume":"2","author":"RJ DeBerardinis","year":"2016","unstructured":"DeBerardinis RJ, Chandel NS. Fundamentals of cancer metabolism. Sci Adv. 2016;2:e1600200.","journal-title":"Sci Adv"},{"key":"6775_CR41","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.cmet.2019.11.010","volume":"31","author":"MT Snaebjornsson","year":"2020","unstructured":"Snaebjornsson MT, Janaki-Raman S, Schulze A. Greasing the wheels of the cancer machine: the role of lipid metabolism in cancer. Cell Metab. 2020;31:62\u201376.","journal-title":"Cell Metab"},{"key":"6775_CR42","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1016\/j.biochi.2004.09.018","volume":"86","author":"D Eberl\u00e9","year":"2004","unstructured":"Eberl\u00e9 D, Hegarty B, Bossard P, Ferr\u00e9 P, Foufelle F. SREBP transcription factors: master regulators of lipid homeostasis. Biochimie. 2004;86:839\u201348.","journal-title":"Biochimie"},{"key":"6775_CR43","doi-asserted-by":"publisher","first-page":"12027","DOI":"10.1073\/pnas.1534923100","volume":"100","author":"JD Horton","year":"2003","unstructured":"Horton JD, Shah NA, Warrington JA, Anderson NN, Park SW, Brown MS, et al. Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes. Proc Natl Acad Sci USA. 2003;100:12027\u201332.","journal-title":"Proc Natl Acad Sci USA"},{"key":"6775_CR44","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2023.121698","volume":"327","author":"X Zhou","year":"2023","unstructured":"Zhou X, Li Y, Yang C, Chen D, Wang T, Liu T, et al. Cordycepin reprogramming lipid metabolism to block metastasis and EMT via ERO1A\/mTOR\/SREBP1 axis in cholangiocarcinoma. Life Sci. 2023;327:121698.","journal-title":"Life Sci"},{"key":"6775_CR45","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1038\/s41571-022-00601-9","volume":"19","author":"H Yamaguchi","year":"2022","unstructured":"Yamaguchi H, Hsu JM, Yang WH, Hung MC. Mechanisms regulating PD-L1 expression in cancers and associated opportunities for novel small-molecule therapeutics. Nat Rev Clin Oncol. 2022;19:287\u2013305.","journal-title":"Nat Rev Clin Oncol"},{"key":"6775_CR46","doi-asserted-by":"publisher","first-page":"2093","DOI":"10.1136\/gutjnl-2021-326259","volume":"71","author":"J Leslie","year":"2022","unstructured":"Leslie J, Mackey JBG, Jamieson T, Ramon-Gil E, Drake TM, Fercoq F, et al. CXCR2 inhibition enables NASH-HCC immunotherapy. Gut. 2022;71:2093\u2013106.","journal-title":"Gut"},{"key":"6775_CR47","doi-asserted-by":"publisher","first-page":"1224","DOI":"10.3892\/or.2020.7667","volume":"44","author":"R Zhang","year":"2020","unstructured":"Zhang R, Chen X, Fu S, Xu L, Lin J. A small molecule STAT3 inhibitor, LLL12, enhances cisplatin\u2011 and paclitaxel\u2011mediated inhibition of cell growth and migration in human ovarian cancer cells. Oncol Rep. 2020;44:1224\u201332.","journal-title":"Oncol Rep"},{"key":"6775_CR48","doi-asserted-by":"publisher","first-page":"5369","DOI":"10.7150\/ijbs.73949","volume":"18","author":"H Cao","year":"2022","unstructured":"Cao H, Huang T, Dai M, Kong X, Liu H, Zheng Z, et al. Tumor microenvironment and its implications for antitumor immunity in cholangiocarcinoma: future perspectives for novel therapies. Int J Biol Sci. 2022;18:5369\u201390.","journal-title":"Int J Biol Sci"},{"key":"6775_CR49","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1002\/hep.32317","volume":"77","author":"Y Shiode","year":"2023","unstructured":"Shiode Y, Kodama T, Shigeno S, Murai K, Tanaka S, Newberg JY, et al. TNF receptor-related factor 3 inactivation promotes the development of intrahepatic cholangiocarcinoma through NF-\u03baB-inducing kinase-mediated hepatocyte transdifferentiation. Hepatology. 2023;77:395\u2013410.","journal-title":"Hepatology"},{"key":"6775_CR50","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1038\/s41392-021-00572-w","volume":"6","author":"L Zhong","year":"2021","unstructured":"Zhong L, Li Y, Xiong L, Wang W, Wu M, Yuan T, et al. Small molecules in targeted cancer therapy: advances, challenges, and future perspectives. Signal Transduct Target Ther. 2021;6:201.","journal-title":"Signal Transduct Target Ther"},{"key":"6775_CR51","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1016\/S0140-6736(20)30164-1","volume":"395","author":"PL Bedard","year":"2020","unstructured":"Bedard PL, Hyman DM, Davids MS, Siu LL. Small molecules, big impact: 20 years of targeted therapy in oncology. Lancet. 2020;395:1078\u201388.","journal-title":"Lancet"},{"key":"6775_CR52","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1002\/mds.21226","volume":"22","author":"CG Goetz","year":"2007","unstructured":"Goetz CG, Damier P, Hicking C, Laska E, M\u00fcller T, Olanow CW, et al. Sarizotan as a treatment for dyskinesias in Parkinson\u2019s disease: a double-blind placebo-controlled trial. Mov Disord Off J Mov Disord Soc. 2007;22:179\u201386.","journal-title":"Mov Disord Off J Mov Disord Soc"}],"container-title":["Cell Death &amp; Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41419-024-06775-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-024-06775-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-024-06775-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T09:03:29Z","timestamp":1718183009000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41419-024-06775-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,12]]},"references-count":52,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["6775"],"URL":"https:\/\/doi.org\/10.1038\/s41419-024-06775-7","relation":{},"ISSN":["2041-4889"],"issn-type":[{"value":"2041-4889","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,12]]},"assertion":[{"value":"6 October 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 May 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 May 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 June 2024","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"All in vivo animal experiments were approved by the Committee on the Ethics of Animal Experiments of Nanjing Medical University.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}],"article-number":"411"}}