{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T12:14:58Z","timestamp":1772021698894,"version":"3.50.1"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"vor","delay-in-days":26,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82404772"],"award-info":[{"award-number":["82404772"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82204518"],"award-info":[{"award-number":["82204518"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["QN25H310013"],"award-info":[{"award-number":["QN25H310013"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Commun Signal"],"DOI":"10.1186\/s12964-026-02688-4","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T03:45:39Z","timestamp":1769744739000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Osimertinib activates TFEB to trigger hepatocyte cytoplasmic vacuolation-associated cell death"],"prefix":"10.1186","volume":"24","author":[{"given":"Yueping","family":"Qiu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yijie","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haiying","family":"Ding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenxiu","family":"Xin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuanghui","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qinjie","family":"Weng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiajia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luo","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"issue":"1","key":"2688_CR1","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1186\/s13045-022-01391-4","volume":"15","author":"K Fu","year":"2022","unstructured":"Fu K, et al. Therapeutic strategies for EGFR-mutated non-small cell lung cancer patients with osimertinib resistance. J Hematol Oncol. 2022;15(1):173.","journal-title":"J Hematol Oncol"},{"issue":"17","key":"2688_CR2","doi-asserted-by":"publisher","first-page":"3340","DOI":"10.1158\/1078-0432.CCR-22-3146","volume":"29","author":"JE Gray","year":"2023","unstructured":"Gray JE, et al. Early clearance of plasma epidermal growth factor receptor mutations as a predictor of outcome on osimertinib in advanced Non-Small cell lung Cancer; exploratory analysis from AURA3 and FLAURA. Clin Cancer Res. 2023;29(17):3340\u201351.","journal-title":"Clin Cancer Res"},{"key":"2688_CR3","doi-asserted-by":"publisher","first-page":"672233","DOI":"10.3389\/fphar.2021.672233","volume":"12","author":"C Gianni","year":"2021","unstructured":"Gianni C, et al. Case report: Stevens-Johnson syndrome and hepatotoxicity induced by osimertinib sequential to pembrolizumab in a patient with EGFR-Mutated lung adenocarcinoma. Front Pharmacol. 2021;12:672233.","journal-title":"Front Pharmacol"},{"issue":"4","key":"2688_CR4","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1111\/1759-7714.13363","volume":"11","author":"O Yamaguchi","year":"2020","unstructured":"Yamaguchi O, et al. Severe hepatotoxicity due to osimertinib after nivolumab therapy in patients with non-small cell lung cancer harboring EGFR mutation. Thorac Cancer. 2020;11(4):1045\u201351.","journal-title":"Thorac Cancer"},{"issue":"3","key":"2688_CR5","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1007\/s10565-012-9212-3","volume":"28","author":"T Aki","year":"2012","unstructured":"Aki T, Nara A, Uemura K. Cytoplasmic vacuolization during exposure to drugs and other substances. Cell Biol Toxicol. 2012;28(3):125\u201331.","journal-title":"Cell Biol Toxicol"},{"issue":"3","key":"2688_CR6","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1038\/s41419-019-1360-4","volume":"10","author":"MJ Seo","year":"2019","unstructured":"Seo MJ, et al. Gambogic acid triggers vacuolization-associated cell death in cancer cells via disruption of thiol proteostasis. Cell Death Dis. 2019;10(3):187.","journal-title":"Cell Death Dis"},{"issue":"6","key":"2688_CR7","doi-asserted-by":"publisher","first-page":"2978","DOI":"10.1172\/JCI132366","volume":"130","author":"J Nah","year":"2020","unstructured":"Nah J, et al. Upregulation of Rubicon promotes autosis during myocardial ischemia\/reperfusion injury. J Clin Invest. 2020;130(6):2978\u201391.","journal-title":"J Clin Invest"},{"issue":"5","key":"2688_CR8","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1038\/s41419-024-06750-2","volume":"15","author":"P Depierre","year":"2024","unstructured":"Depierre P, et al. Neuronal autosis is Na(+)\/K(+)-ATPase alpha 3-dependent and involved in hypoxic-ischemic neuronal death. Cell Death Dis. 2024;15(5):363.","journal-title":"Cell Death Dis"},{"issue":"2","key":"2688_CR9","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1038\/s41401-023-01159-7","volume":"45","author":"CC Xu","year":"2024","unstructured":"Xu CC, et al. Paraptosis: a non-classical paradigm of cell death for cancer therapy. Acta Pharmacol Sin. 2024;45(2):223\u201337.","journal-title":"Acta Pharmacol Sin"},{"issue":"10","key":"2688_CR10","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1016\/j.ccell.2022.08.016","volume":"40","author":"JK Mandula","year":"2022","unstructured":"Mandula JK, et al. Ablation of the Endoplasmic reticulum stress kinase PERK induces paraptosis and type I interferon to promote anti-tumor T cell responses. Cancer Cell. 2022;40(10):1145\u2013e11609.","journal-title":"Cancer Cell"},{"key":"2688_CR11","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.brainres.2012.10.056","volume":"1490","author":"T Funakoshi","year":"2013","unstructured":"Funakoshi T, et al. Lysosome vacuolation disrupts the completion of autophagy during norephedrine exposure in SH-SY5Y human neuroblastoma cells. Brain Res. 2013;1490:9\u201322.","journal-title":"Brain Res"},{"issue":"38","key":"2688_CR12","doi-asserted-by":"publisher","first-page":"e2404693","DOI":"10.1002\/advs.202404693","volume":"11","author":"Y Luo","year":"2024","unstructured":"Luo Y, et al. Methuosis inducer SGI-1027 cooperates with everolimus to promote apoptosis and pyroptosis by triggering lysosomal membrane permeability in renal cancer. Adv Sci (Weinh). 2024;11(38):e2404693.","journal-title":"Adv Sci (Weinh)"},{"issue":"7948","key":"2688_CR13","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1038\/s41586-022-05652-7","volume":"614","author":"Z Cui","year":"2023","unstructured":"Cui Z, et al. Structure of the lysosomal mTORC1-TFEB-Rag-Ragulator megacomplex. Nature. 2023;614(7948):572\u20139.","journal-title":"Nature"},{"issue":"8","key":"2688_CR14","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.1038\/s41418-022-01028-6","volume":"29","author":"A Tan","year":"2022","unstructured":"Tan A, et al. Past, present, and future perspectives of transcription factor EB (TFEB): mechanisms of regulation and association with disease. Cell Death Differ. 2022;29(8):1433\u201349.","journal-title":"Cell Death Differ"},{"issue":"3","key":"2688_CR15","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1053\/j.gastro.2018.05.027","volume":"155","author":"X Chao","year":"2018","unstructured":"Chao X, et al. Impaired TFEB-Mediated lysosome biogenesis and autophagy promote chronic Ethanol-Induced liver injury and steatosis in mice. Gastroenterology. 2018;155(3):865\u2013e87912.","journal-title":"Gastroenterology"},{"issue":"10","key":"2688_CR16","doi-asserted-by":"publisher","first-page":"1950","DOI":"10.1111\/acer.14695","volume":"45","author":"X Chao","year":"2021","unstructured":"Chao X, et al. Trehalose activates hepatic transcription factor EB (TFEB) but fails to ameliorate alcohol-impaired TFEB and liver injury in mice. Alcohol Clin Exp Res. 2021;45(10):1950\u201364.","journal-title":"Alcohol Clin Exp Res"},{"issue":"10","key":"2688_CR17","doi-asserted-by":"publisher","first-page":"3221","DOI":"10.1080\/15548627.2020.1851492","volume":"17","author":"P Luo","year":"2021","unstructured":"Luo P, et al. PLK1 (polo like kinase 1)-dependent autophagy facilitates gefitinib-induced hepatotoxicity by degrading COX6A1 (cytochrome c oxidase subunit 6A1). Autophagy. 2021;17(10):3221\u201337.","journal-title":"Autophagy"},{"issue":"8","key":"2688_CR18","doi-asserted-by":"publisher","first-page":"2921","DOI":"10.1007\/s00204-016-1918-1","volume":"91","author":"J Zhang","year":"2017","unstructured":"Zhang J, et al. Effects of 31 FDA approved small-molecule kinase inhibitors on isolated rat liver mitochondria. Arch Toxicol. 2017;91(8):2921\u201338.","journal-title":"Arch Toxicol"},{"issue":"1","key":"2688_CR19","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/s40659-019-0243-6","volume":"52","author":"L Liu","year":"2019","unstructured":"Liu L, et al. Berberine in combination with cisplatin induces necroptosis and apoptosis in ovarian cancer cells. Biol Res. 2019;52(1):37.","journal-title":"Biol Res"},{"issue":"1","key":"2688_CR20","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1038\/s41420-023-01632-6","volume":"9","author":"L Hu","year":"2023","unstructured":"Hu L, et al. Osimertinib induces paraptosis and TRIP13 confers resistance in glioblastoma cells. Cell Death Discov. 2023;9(1):333.","journal-title":"Cell Death Discov"},{"key":"2688_CR21","doi-asserted-by":"publisher","first-page":"105582","DOI":"10.1016\/j.phrs.2021.105582","volume":"168","author":"PMP Ferreira","year":"2021","unstructured":"Ferreira PMP, et al. Chloroquine and hydroxychloroquine in antitumor therapies based on autophagy-related mechanisms. Pharmacol Res. 2021;168:105582.","journal-title":"Pharmacol Res"},{"issue":"4","key":"2688_CR22","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.1152\/physrev.00047.2011","volume":"92","author":"SC Lu","year":"2012","unstructured":"Lu SC, Mato JM. -adenosylmethionine in liver health, injury, and cancer. Physiol Rev. 2012;92(4):1515\u201342.","journal-title":"Physiol Rev"},{"issue":"8","key":"2688_CR23","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1097\/MEG.0000000000001141","volume":"30","author":"SI Mora","year":"2018","unstructured":"Mora SI, et al. Chronic liver diseases and the potential use of S-adenosyl-L-methionine as a hepatoprotector. Eur J Gastroenterol Hepatol. 2018;30(8):893\u2013900.","journal-title":"Eur J Gastroenterol Hepatol"},{"issue":"5","key":"2688_CR24","doi-asserted-by":"publisher","first-page":"1306","DOI":"10.1002\/hep.21650","volume":"45","author":"JM Mato","year":"2007","unstructured":"Mato JM, Lu SC. Role of s-adenosyl-L-methionine in liver health and injury. Hepatology. 2007;45(5):1306\u201312.","journal-title":"Hepatology"},{"issue":"20","key":"2688_CR25","doi-asserted-by":"publisher","first-page":"14032","DOI":"10.1021\/acs.jmedchem.2c01246","volume":"65","author":"F Xu","year":"2022","unstructured":"Xu F, et al. Discovery of Isoform-Selective Akt3 degraders overcoming Osimertinib-Induced resistance in Non-Small cell lung cancer cells. J Med Chem. 2022;65(20):14032\u201348.","journal-title":"J Med Chem"},{"issue":"51","key":"2688_CR26","doi-asserted-by":"publisher","first-page":"20364","DOI":"10.1073\/pnas.1319661110","volume":"110","author":"Y Liu","year":"2013","unstructured":"Liu Y, et al. Autosis is a Na+,K+-ATPase-regulated form of cell death triggered by autophagy-inducing peptides, starvation, and hypoxia-ischemia. Proc Natl Acad Sci U S A. 2013;110(51):20364\u201371.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"2688_CR27","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.1016\/j.ajpath.2014.02.028","volume":"184","author":"WA Maltese","year":"2014","unstructured":"Maltese WA, Overmeyer JH. Methuosis: nonapoptotic cell death associated with vacuolization of macropinosome and endosome compartments. Am J Pathol. 2014;184(6):1630\u201342.","journal-title":"Am J Pathol"},{"issue":"1","key":"2688_CR28","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1186\/s13046-023-02922-8","volume":"42","author":"D Kim","year":"2023","unstructured":"Kim D, et al. Nutlin-3a induces KRAS mutant\/p53 wild type lung cancer specific methuosis-like cell death that is dependent on GFPT2. J Exp Clin Cancer Res. 2023;42(1):338.","journal-title":"J Exp Clin Cancer Res"},{"key":"2688_CR29","doi-asserted-by":"publisher","first-page":"1274076","DOI":"10.3389\/fphar.2023.1274076","volume":"14","author":"S Hanson","year":"2023","unstructured":"Hanson S, et al. Corrigendum: paraptosis: a unique cell death mode for targeting cancer. Front Pharmacol. 2023;14:1274076.","journal-title":"Front Pharmacol"},{"issue":"5","key":"2688_CR30","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1111\/cas.70013","volume":"116","author":"X Wen","year":"2025","unstructured":"Wen X, Ma H. Cytoplasmic vacuolization: a fascinating morphological alteration from cellular stress to cell death. Cancer Sci. 2025;116(5):1181\u201392.","journal-title":"Cancer Sci"},{"key":"2688_CR31","doi-asserted-by":"publisher","first-page":"104298","DOI":"10.1016\/j.critrevonc.2024.104298","volume":"196","author":"Z Wang","year":"2024","unstructured":"Wang Z, et al. Higher risk of hepatotoxicity associated with Cabozantinib in cancer patients. Crit Rev Oncol Hematol. 2024;196:104298.","journal-title":"Crit Rev Oncol Hematol"},{"issue":"6","key":"2688_CR32","doi-asserted-by":"publisher","first-page":"2105","DOI":"10.1002\/med.21577","volume":"39","author":"MN Paludetto","year":"2019","unstructured":"Paludetto MN, et al. Identifying the reactive metabolites of tyrosine kinase inhibitors in a comprehensive approach: implications for drug-drug interactions and hepatotoxicity. Med Res Rev. 2019;39(6):2105\u201352.","journal-title":"Med Res Rev"},{"issue":"1","key":"2688_CR33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/15548627.2020.1797280","volume":"17","author":"DJ Klionsky","year":"2021","unstructured":"Klionsky DJ, et al. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)(1). Autophagy. 2021;17(1):1\u2013382.","journal-title":"Autophagy"},{"issue":"15","key":"2688_CR34","doi-asserted-by":"publisher","first-page":"2271","DOI":"10.1111\/1759-7714.14556","volume":"13","author":"YL Cheng","year":"2022","unstructured":"Cheng YL, et al. Osimertinib-related liver injury with successful osimertinib rechallenge: A case report. Thorac Cancer. 2022;13(15):2271\u20134.","journal-title":"Thorac Cancer"},{"issue":"12","key":"2688_CR35","doi-asserted-by":"publisher","first-page":"2677","DOI":"10.1080\/15548627.2024.2384348","volume":"20","author":"J Wang","year":"2024","unstructured":"Wang J, et al. Preserving mitochondrial homeostasis protects against drug-induced liver injury via inducing OPTN (optineurin)-dependent mitophagy. Autophagy. 2024;20(12):2677\u201396.","journal-title":"Autophagy"},{"issue":"4","key":"2688_CR36","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.1080\/15548627.2022.2117893","volume":"19","author":"J Pan","year":"2023","unstructured":"Pan J, et al. Genome-Scale CRISPR screen identifies LAPTM5 driving lenvatinib resistance in hepatocellular carcinoma. Autophagy. 2023;19(4):1184\u201398.","journal-title":"Autophagy"},{"issue":"11","key":"2688_CR37","doi-asserted-by":"publisher","first-page":"2611","DOI":"10.1021\/acs.accounts.8b00356","volume":"51","author":"WE Broderick","year":"2018","unstructured":"Broderick WE, Hoffman BM, Broderick JB. Mechanism of radical initiation in the radical S-Adenosyl-l-methionine superfamily. Acc Chem Res. 2018;51(11):2611\u20139.","journal-title":"Acc Chem Res"},{"key":"2688_CR38","doi-asserted-by":"publisher","DOI":"10.1039\/d4cc04860a","author":"J Schoning","year":"2024","unstructured":"Schoning J, et al. SAM-III aptamer enables detection of enzymatic SAM analogue generation. Chem Commun (Camb). 2024. https:\/\/doi.org\/10.1039\/d4cc04860a.","journal-title":"Chem Commun (Camb)"},{"issue":"5","key":"2688_CR39","doi-asserted-by":"publisher","first-page":"S1183","DOI":"10.1093\/ajcn\/76.5.1183S","volume":"76","author":"CS Lieber","year":"2002","unstructured":"Lieber CS. S-adenosyl-L-methionine: its role in the treatment of liver disorders. Am J Clin Nutr. 2002;76(5):S1183\u20137.","journal-title":"Am J Clin Nutr"},{"key":"2688_CR40","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12081539","author":"S Valdes","year":"2023","unstructured":"Valdes S, et al. S-adenosylmethionine decreases bacterial translocation, proinflammatory cytokines, oxidative stress and apoptosis markers in hepatic ischemia-reperfusion injury in Wistar rats. Antioxidants (Basel). 2023. https:\/\/doi.org\/10.3390\/antiox12081539.","journal-title":"Antioxidants (Basel)"},{"issue":"2","key":"2688_CR41","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1016\/j.cell.2013.06.041","volume":"154","author":"BM Sutter","year":"2013","unstructured":"Sutter BM, et al. Methionine inhibits autophagy and promotes growth by inducing the SAM-responsive methylation of PP2A. Cell. 2013;154(2):403\u201315.","journal-title":"Cell"},{"issue":"2","key":"2688_CR42","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/j.jhep.2015.08.037","volume":"64","author":"I Zubiete-Franco","year":"2016","unstructured":"Zubiete-Franco I, et al. Methionine and S-adenosylmethionine levels are critical regulators of PP2A activity modulating lipophagy during steatosis. J Hepatol. 2016;64(2):409\u201318.","journal-title":"J Hepatol"}],"container-title":["Cell Communication and Signaling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12964-026-02688-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-026-02688-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-026-02688-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T11:31:55Z","timestamp":1772019115000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12964-026-02688-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,30]]},"references-count":42,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["2688"],"URL":"https:\/\/doi.org\/10.1186\/s12964-026-02688-4","relation":{},"ISSN":["1478-811X"],"issn-type":[{"value":"1478-811X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,30]]},"assertion":[{"value":"8 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"142"}}