{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T14:26:38Z","timestamp":1792506398551,"version":"4.5.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"vor","delay-in-days":49,"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":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Cell Int"],"DOI":"10.1186\/s12935-026-04288-1","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T18:23:15Z","timestamp":1775672595000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Comprehensive pan-cancer analysis of AARS1, a newly identified lactyltransferase in human cancers"],"prefix":"10.1186","volume":"26","author":[{"given":"Tingting","family":"Fu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiye","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengnan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,8]]},"reference":[{"key":"4288_CR1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines13051149","author":"P Sutkowy","year":"2025","unstructured":"Sutkowy P, Czele\u0144 P. Redox balance in cancer in the context of tumor prevention and treatment. Biomedicines. 2025. https:\/\/doi.org\/10.3390\/biomedicines13051149.","journal-title":"Biomedicines"},{"issue":"3","key":"4288_CR2","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229\u201363. https:\/\/doi.org\/10.3322\/caac.21834.","journal-title":"CA Cancer J Clin"},{"key":"4288_CR3","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107753","volume":"221","author":"Y Xiao","year":"2021","unstructured":"Xiao Y, Yu D. Tumor microenvironment as a therapeutic target in cancer. Pharmacol Ther. 2021;221:107753. https:\/\/doi.org\/10.1016\/j.pharmthera.2020.107753.","journal-title":"Pharmacol Ther"},{"key":"4288_CR4","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2022.5471","author":"R Naser","year":"2023","unstructured":"Naser R, Fakhoury I, El-Fouani A, Abi-Habib R, El-Sibai M. Role of the tumor microenvironment in cancer hallmarks and targeted therapy (Review). Int J Oncol. 2023. https:\/\/doi.org\/10.3892\/ijo.2022.5471.","journal-title":"Int J Oncol"},{"issue":"1","key":"4288_CR5","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-024-01682-2","volume":"16","author":"Y Hu","year":"2024","unstructured":"Hu Y, He Z, Li Z, Wang Y, Wu N, Sun H, et al. Lactylation: the novel histone modification influence on gene expression, protein function, and disease. Clin Epigenetics. 2024;16(1):72. https:\/\/doi.org\/10.1186\/s13148-024-01682-2.","journal-title":"Clin Epigenetics"},{"issue":"5","key":"4288_CR6","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1038\/nrc3038","volume":"11","author":"WH Koppenol","year":"2011","unstructured":"Koppenol WH, Bounds PL, Dang CV. Otto Warburg\u2019s contributions to current concepts of cancer metabolism. Nat Rev Cancer. 2011;11(5):325\u201337. https:\/\/doi.org\/10.1038\/nrc3038.","journal-title":"Nat Rev Cancer"},{"issue":"11","key":"4288_CR7","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.1016\/j.ccell.2024.09.006","volume":"42","author":"H Li","year":"2024","unstructured":"Li H, Sun L, Gao P, Hu H. Lactylation in cancer: current understanding and challenges. Cancer Cell. 2024;42(11):1803\u20137. https:\/\/doi.org\/10.1016\/j.ccell.2024.09.006.","journal-title":"Cancer Cell"},{"issue":"16","key":"4288_CR8","doi-asserted-by":"publisher","first-page":"6210","DOI":"10.7150\/ijbs.75434","volume":"18","author":"J Wang","year":"2022","unstructured":"Wang J, Yang P, Yu T, Gao M, Liu D, Zhang J, et al. Lactylation of PKM2 suppresses inflammatory metabolic adaptation in pro-inflammatory macrophages. Int J Biol Sci. 2022;18(16):6210\u201325. https:\/\/doi.org\/10.7150\/ijbs.75434.","journal-title":"Int J Biol Sci"},{"issue":"1","key":"4288_CR9","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42025-8","volume":"14","author":"L Sun","year":"2023","unstructured":"Sun L, Zhang Y, Yang B, Sun S, Zhang P, Luo Z, et al. Lactylation of METTL16 promotes cuproptosis via m(6)A-modification on FDX1 mRNA in gastric cancer. Nat Commun. 2023;14(1):6523. https:\/\/doi.org\/10.1038\/s41467-023-42025-8.","journal-title":"Nat Commun"},{"issue":"2","key":"4288_CR10","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1093\/nar\/gkad1160","volume":"52","author":"J Douglas","year":"2024","unstructured":"Douglas J, Bouckaert R, Carter CW Jr., Wills PR. Enzymic recognition of amino acids drove the evolution of primordial genetic codes. Nucleic Acids Res. 2024;52(2):558\u201371. https:\/\/doi.org\/10.1093\/nar\/gkad1160.","journal-title":"Nucleic Acids Res"},{"issue":"10","key":"4288_CR11","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1016\/j.scib.2024.11.049","volume":"70","author":"S Wang","year":"2025","unstructured":"Wang S, Lv H, Zhou F. AARS1 and AARS2, the L-lactate sensors and universal lactyltransferases. Sci Bull Beijing. 2025;70(10):1547\u20139. https:\/\/doi.org\/10.1016\/j.scib.2024.11.049.","journal-title":"Sci Bull Beijing"},{"issue":"10","key":"4288_CR12","doi-asserted-by":"publisher","first-page":"2375","DOI":"10.1016\/j.cell.2024.04.002","volume":"187","author":"Z Zong","year":"2024","unstructured":"Zong Z, Xie F, Wang S, Wu X, Zhang Z, Yang B, et al. Alanyl-tRNA synthetase, AARS1, is a lactate sensor and lactyltransferase that lactylates p53 and contributes to tumorigenesis. Cell. 2024;187(10):2375-92.e33. https:\/\/doi.org\/10.1016\/j.cell.2024.04.002.","journal-title":"Cell"},{"key":"4288_CR13","doi-asserted-by":"publisher","DOI":"10.1172\/jci174587","author":"J Ju","year":"2024","unstructured":"Ju J, Zhang H, Lin M, Yan Z, An L, Cao Z, et al. The alanyl-tRNA synthetase AARS1 moonlights as a lactyltransferase to promote YAP signaling in gastric cancer. J Clin Invest. 2024. https:\/\/doi.org\/10.1172\/jci174587.","journal-title":"J Clin Invest"},{"issue":"4","key":"4288_CR14","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2025.115545","volume":"44","author":"Z Xing","year":"2025","unstructured":"Xing Z, Yang T, Li X, Xu H, Hong Y, Shao S, et al. High-glucose-associated YTHDC1 lactylation reduces the sensitivity of bladder cancer to enfortumab vedotin therapy. Cell Rep. 2025;44(4):115545. https:\/\/doi.org\/10.1016\/j.celrep.2025.115545.","journal-title":"Cell Rep"},{"issue":"5897","key":"4288_CR15","doi-asserted-by":"publisher","first-page":"1801","DOI":"10.1126\/science.1164368","volume":"321","author":"S Jones","year":"2008","unstructured":"Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, Angenendt P, et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science. 2008;321(5897):1801\u20136. https:\/\/doi.org\/10.1126\/science.1164368.","journal-title":"Science"},{"issue":"3","key":"4288_CR16","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1093\/oxfordjournals.bmb.a072911","volume":"50","author":"DP Lane","year":"1994","unstructured":"Lane DP. p53 and human cancers. Br Med Bull. 1994;50(3):582\u201399. https:\/\/doi.org\/10.1093\/oxfordjournals.bmb.a072911.","journal-title":"Br Med Bull"},{"issue":"1","key":"4288_CR17","doi-asserted-by":"publisher","DOI":"10.1186\/s40170-023-00312-4","volume":"11","author":"W Zhuang","year":"2023","unstructured":"Zhuang W, Shi X, Gao S, Qin X. Restoring gluconeogenesis by TEF inhibited proliferation and promoted apoptosis and immune surveillance in kidney renal clear cell carcinoma. Cancer Metab. 2023;11(1):11. https:\/\/doi.org\/10.1186\/s40170-023-00312-4.","journal-title":"Cancer Metab"},{"issue":"7","key":"4288_CR18","doi-asserted-by":"publisher","first-page":"1592","DOI":"10.1158\/0008-5472.Can-17-1751","volume":"78","author":"R Yonashiro","year":"2018","unstructured":"Yonashiro R, Eguchi K, Wake M, Takeda N, Nakayama K. Pyruvate dehydrogenase PDH-E1\u03b2 controls tumor progression by altering the metabolic status of cancer cells. Cancer Res. 2018;78(7):1592\u2013603. https:\/\/doi.org\/10.1158\/0008-5472.Can-17-1751.","journal-title":"Cancer Res"},{"key":"4288_CR19","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.ymeth.2016.11.014","volume":"113","author":"P Fang","year":"2017","unstructured":"Fang P, Guo M. Structural characterization of human aminoacyl-tRNA synthetases for translational and nontranslational functions. Methods. 2017;113:83\u201390. https:\/\/doi.org\/10.1016\/j.ymeth.2016.11.014.","journal-title":"Methods"},{"issue":"12","key":"4288_CR20","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1002\/iub.2911","volume":"76","author":"J Douglas","year":"2024","unstructured":"Douglas J, Cui H, Perona JJ, Vargas-Rodriguez O, Tyynismaa H, Carre\u00f1o CA, et al. AARS Online: a collaborative database on the structure, function, and evolution of the aminoacyl-tRNA synthetases. IUBMB Life. 2024;76(12):1091\u2013105. https:\/\/doi.org\/10.1002\/iub.2911.","journal-title":"IUBMB Life"},{"key":"4288_CR21","doi-asserted-by":"publisher","DOI":"10.1017\/erm.2022.42","volume":"25","author":"X Lv","year":"2023","unstructured":"Lv X, Lv Y, Dai X. Lactate, histone lactylation and cancer hallmarks. Expert Rev Mol Med. 2023;25:e7. https:\/\/doi.org\/10.1017\/erm.2022.42.","journal-title":"Expert Rev Mol Med"},{"issue":"4","key":"4288_CR22","doi-asserted-by":"publisher","first-page":"E330","DOI":"10.1152\/ajpendo.00159.2022","volume":"324","author":"H Fan","year":"2023","unstructured":"Fan H, Yang F, Xiao Z, Luo H, Chen H, Chen Z, et al. Lactylation: novel epigenetic regulatory and therapeutic opportunities. Am J Physiol Endocrinol Metab. 2023;324(4):E330\u20138. https:\/\/doi.org\/10.1152\/ajpendo.00159.2022.","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"4","key":"4288_CR23","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1038\/s41556-025-01635-8","volume":"27","author":"Z Zong","year":"2025","unstructured":"Zong Z, Ren J, Yang B, Zhang L, Zhou F. Emerging roles of lysine lactyltransferases and lactylation. Nat Cell Biol. 2025;27(4):563\u201374. https:\/\/doi.org\/10.1038\/s41556-025-01635-8.","journal-title":"Nat Cell Biol"},{"key":"4288_CR24","doi-asserted-by":"publisher","DOI":"10.1111\/jop.70058","author":"S Chen","year":"2025","unstructured":"Chen S, You Y, Zhu F, Zhang Z, Shi J, Tian Z. AARS1 Implicates Malignancy and Immune Infiltration in Head and Neck Squamous Cell Carcinoma, Serving as a Prognostic Predictor. J Oral Pathol Med. 2025. https:\/\/doi.org\/10.1111\/jop.70058.","journal-title":"J Oral Pathol Med"},{"key":"4288_CR25","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/ioaf188","author":"L Liu","year":"2025","unstructured":"Liu L, Du S, Liu J, Wang M, Ge X, Yue C, et al. AARS1 promotes endometriosis progression by promoting the lactylation of Snail1. Biol Reprod. 2025. https:\/\/doi.org\/10.1093\/biolre\/ioaf188.","journal-title":"Biol Reprod"},{"issue":"7","key":"4288_CR26","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1038\/nrg3230","volume":"13","author":"PA Jones","year":"2012","unstructured":"Jones PA. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet. 2012;13(7):484\u201392. https:\/\/doi.org\/10.1038\/nrg3230.","journal-title":"Nat Rev Genet"},{"issue":"4","key":"4288_CR27","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.70294","volume":"15","author":"Q Yang","year":"2025","unstructured":"Yang Q, Guo C, Zhang L. The role of metabolite sensors in metabolism-immune interaction: New targets for immune modulation. Clin Transl Med. 2025;15(4):e70294. https:\/\/doi.org\/10.1002\/ctm2.70294.","journal-title":"Clin Transl Med"},{"issue":"1","key":"4288_CR28","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1186\/s12883-022-02828-6","volume":"22","author":"H H\u00f8yer","year":"2022","unstructured":"H\u00f8yer H, Busk \u00d8L, Esbensen QY, R\u00f8sby O, Hilmarsen HT, Russell MB, et al. Clinical characteristics and proteome modifications in two Charcot-Marie-Tooth families with the AARS1 Arg326Trp mutation. BMC Neurol. 2022;22(1):299. https:\/\/doi.org\/10.1186\/s12883-022-02828-6.","journal-title":"BMC Neurol"},{"issue":"12","key":"4288_CR29","doi-asserted-by":"publisher","first-page":"2352","DOI":"10.1038\/s41436-021-01286-8","volume":"23","author":"G Helman","year":"2021","unstructured":"Helman G, Mendes MI, Nicita F, Darbelli L, Sherbini O, Moore T, et al. Expanded phenotype of AARS1-related white matter disease. Genet Med. 2021;23(12):2352\u20139. https:\/\/doi.org\/10.1038\/s41436-021-01286-8.","journal-title":"Genet Med"},{"key":"4288_CR30","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202509477","author":"H Han","year":"2025","unstructured":"Han H, Wang S, Ma L, Yin H, Cheng X, Wang Y, et al. ASH2L-K312-Lac stimulates angiogenesis in tumors to expedite the malignant progression of hepatocellular carcinoma. Adv Sci. 2025. https:\/\/doi.org\/10.1002\/advs.202509477.","journal-title":"Adv Sci"},{"issue":"1","key":"4288_CR31","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1038\/s41392-025-02302-y","volume":"10","author":"X Li","year":"2025","unstructured":"Li X, Zhang C, Mei Y, Zhong W, Fan W, Liu L, et al. Irinotecan alleviates chemoresistance to anthracyclines through the inhibition of AARS1-mediated BLM lactylation and homologous recombination repair. Signal Transduct Target Ther. 2025;10(1):214. https:\/\/doi.org\/10.1038\/s41392-025-02302-y.","journal-title":"Signal Transduct Target Ther"},{"issue":"33","key":"4288_CR32","doi-asserted-by":"publisher","first-page":"11822","DOI":"10.1074\/jbc.RA120.014505","volume":"295","author":"M Zoabi","year":"2020","unstructured":"Zoabi M, Zhang L, Li TM, Elias JE, Carlson SM, Gozani O. Methyltransferase-like 21C (METTL21C) methylates alanine tRNA synthetase at Lys-943 in muscle tissue. J Biol Chem. 2020;295(33):11822\u201332. https:\/\/doi.org\/10.1074\/jbc.RA120.014505.","journal-title":"J Biol Chem"},{"issue":"1","key":"4288_CR33","doi-asserted-by":"publisher","first-page":"2469746","DOI":"10.1080\/0886022x.2025.2469746","volume":"47","author":"Y Cheng","year":"2025","unstructured":"Cheng Y, Guo L. Lactate metabolism and lactylation in kidney diseases: insights into mechanisms and therapeutic opportunities. Ren Fail. 2025;47(1):2469746. https:\/\/doi.org\/10.1080\/0886022x.2025.2469746.","journal-title":"Ren Fail"},{"issue":"Pt 1","key":"4288_CR34","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2025.146571","volume":"322","author":"Y Tang","year":"2025","unstructured":"Tang Y, Dai C, Yang H, Yang X, Chen Z, Dou J, et al. KAT8-mediated MDH2 lactylation promotes renal cancer progression by enhancing mitochondrial function and stress resistance. Int J Biol Macromol. 2025;322(Pt 1):146571. https:\/\/doi.org\/10.1016\/j.ijbiomac.2025.146571.","journal-title":"Int J Biol Macromol"},{"issue":"11","key":"4288_CR35","doi-asserted-by":"publisher","first-page":"e23219","DOI":"10.1096\/fj.202202024RR","volume":"37","author":"S Gupta","year":"2023","unstructured":"Gupta S, Jani J, Vijayasurya N, Mochi J, Tabasum S, Sabarwal A, et al. Aminoacyl-tRNA synthetase - a molecular multitasker. Faseb J. 2023;37(11):e23219. https:\/\/doi.org\/10.1096\/fj.202202024RR.","journal-title":"Faseb J."},{"issue":"8036","key":"4288_CR36","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1038\/s41586-024-07992-y","volume":"634","author":"H Li","year":"2024","unstructured":"Li H, Liu C, Li R, Zhou L, Ran Y, Yang Q, et al. AARS1 and AARS2 sense L-lactate to regulate cGAS as global lysine lactyltransferases. Nature. 2024;634(8036):1229\u201337. https:\/\/doi.org\/10.1038\/s41586-024-07992-y.","journal-title":"Nature"}],"container-title":["Cancer Cell International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12935-026-04288-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12935-026-04288-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12935-026-04288-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T01:35:45Z","timestamp":1779845745000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12935-026-04288-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,8]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4288"],"URL":"https:\/\/doi.org\/10.1186\/s12935-026-04288-1","relation":{},"ISSN":["1475-2867"],"issn-type":[{"value":"1475-2867","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,8]]},"assertion":[{"value":"8 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 April 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":"Human tissue samples were obtained from five patients with ccRCC (tumor tissues and matched adjacent noncancerous kidney tissues) and five patients with LUAD (tumor tissues and matched adjacent noncancerous lung tissues) who underwent surgical resection at Shandong Provincial Hospital Affiliated to Shandong First Medical University. The study protocol was approved by the Institutional Review Board\/Ethics Committee of Shandong Provincial Hospital (approval numbers: NSFC-2021\u2013099 and NSFC-2023\u2013225), and written informed consent was obtained from all participants prior to sample collection.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"207"}}