{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T04:13:19Z","timestamp":1784261599741,"version":"3.55.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T00:00:00Z","timestamp":1749081600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The effects exerted by the TEA domain transcription factor family genes on tumorigenesis in various cancers have been extensively investigated. Nevertheless, the potential role of TEAD1 in cancer-related epigenetic alterations, immunological characteristics, and prognosis remains ambiguous. This study aims to clarify the function and potential mechanisms of action of TEAD1 in cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We assessed pan-cancer expression, methylation, and mutation profiles of TEAD1 to determine its prognostic significance in clinical settings. Furthermore, we analyzed the pan-cancer immunological landscape of TEAD1, with a particular focus on liver hepatocellular carcinoma (LIHC), using correlation analysis. We also performed a subtype-specific analysis of TEAD1 in LIHC to identify its expression patterns, immunological traits, and constructed a prognostic model based on disulfidptosis-related genes. Lastly, we assessed the impact of TEAD1 knockdown on LIHC cell lines HepG2 and Huh-7 by using <jats:italic>in vitro<\/jats:italic> experiments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our findings suggest that TEAD1 is differentially expressed across various cancer types and can act as an independent prognostic factor for multiple cancers. Moreover, we observed that epigenetic changes involving TEAD1 are highly heterogeneous among several cancers; abnormal methylation and copy number variations were associated with a poor prognosis in multiple malignancies, especially in LIHC. Immunoassays demonstrated a significant association between TEAD1 and numerous immune checkpoints in LIHC. Additionally, cellular experiments revealed that knocking down TEAD1 reduced the proliferation, migration, and invasion capabilities of LIHC cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The results of this study imply that TEAD1 may serve as a promising prognostic biomarker for tumors and an immunotherapy target, while playing a crucial role in the proliferation, migration, and invasion processes within LIHC.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1567969","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T10:13:48Z","timestamp":1749118428000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Dissecting the multi-omics landscape of TEAD1 in hepatocellular carcinoma: cycle regulation and metastatic potential"],"prefix":"10.3389","volume":"16","author":[{"given":"Ruiping","family":"Huai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Canquan","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28770","article-title":"Patient-reported barriers are associated with lower hepatocellular carcinoma surveillance rates in patients with cirrhosis","volume":"65","author":"Farvardin","year":"2017","journal-title":"Hepatology"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.14.8260","article-title":"DTEF-1, a novel member of the transcription enhancer factor-1 (TEF-1) multigene family","volume":"271","author":"Azakie","year":"1996","journal-title":"J Biol Chem"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0607171103","article-title":"Insights into transcription enhancer factor 1 (TEF-1) activity from the solution structure of the TEA domain","volume":"103","author":"Anbanandam","year":"2006","journal-title":"Proc Natl Acad Sci USA"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.20.12928","article-title":"Human TEF-5 is preferentially expressed in placenta and binds to multiple functional elements of the human chorionic somatomammotropin-B gene enhancer","volume":"272","author":"Jacquemin","year":"1997","journal-title":"J Biol Chem"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.36.21775","article-title":"A novel family of developmentally regulated mammalian transcription factors containing the TEA\/ATTS DNA binding domain","volume":"271","author":"Jacquemin","year":"1996","journal-title":"J Biol Chem"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1987.tb02606.x","article-title":"One cell-specific and three ubiquitous nuclear proteins bind in vitro to overlapping motifs in the domain B1 of the SV40 enhancer","volume":"6","author":"Xiao","year":"1987","journal-title":"EMBO J"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2017.257","article-title":"TEAD1\/4 exerts oncogenic role and is negatively regulated by miR-4269 in gastric tumorigenesis","volume":"36","author":"Zhou","year":"2017","journal-title":"Oncogene"},{"key":"B9","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1007\/s10565-024-09863-8","article-title":"MKLN1-AS promotes pancreatic cancer progression as a crucial downstream mediator of HIF-1\u03b1 through miR-185-5p\/TEAD1 pathway","volume":"40","author":"Chen","year":"2024","journal-title":"Cell Biol Toxicol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1038\/s41419-024-06666-x","article-title":"ACAT2 suppresses the ubiquitination of YAP1 to enhance the proliferation and metastasis ability of gastric cancer via the upregulation of SETD7","volume":"15","author":"Zhang","year":"2024","journal-title":"Cell Death Dis"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3772","article-title":"Toil enables reproducible, open source, big biomedical data analyses","volume":"35","author":"Vivian","year":"2017","journal-title":"Nat Biotechnol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"2612","DOI":"10.1038\/ncomms3612","article-title":"Inferring tumour purity and stromal and immune cell admixture from expression data","volume":"4","author":"Yoshihara","year":"2013","journal-title":"Nat Commun"},{"key":"B13","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1186\/s13059-017-1349-1","article-title":"xCell: digitally portraying the tissue cellular heterogeneity landscape","volume":"18","author":"Aran","year":"2017","journal-title":"Genome Biol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/nature08460","article-title":"Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1","volume":"462","author":"Barbie","year":"2009","journal-title":"Nature"},{"key":"B15","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1186\/s13059-016-1070-5","article-title":"Estimating the population abundance of tissue-infiltrating immune and stromal cell populations using gene expression","volume":"17","author":"Becht","year":"2016","journal-title":"Genome Biol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.12.019","article-title":"Pan-cancer immunogenomic analyses reveal genotype-immunophenotype relationships and predictors of response to checkpoint blockade","volume":"18","author":"Charoentong","year":"2017","journal-title":"Cell Rep"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-18-0689","article-title":"TIP: A web server for resolving tumor immunophenotype profiling","volume":"78","author":"Xu","year":"2018","journal-title":"Cancer Res"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac959","article-title":"TISCH2: expanded datasets and new tools for single-cell transcriptome analyses of the tumor microenvironment","volume":"51","author":"Han","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"B19","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1038\/s41467-023-36560-7","article-title":"Reconstruction of the tumor spatial microenvironment along the Malignant-boundary-nonmalignant axis","volume":"14","author":"Xun","year":"2023","journal-title":"Nat Commun"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1205250","article-title":"Identification of disulfidptosis related subtypes, characterization of tumor microenvironment infiltration, and development of DRG prognostic prediction model in RCC, in which MSH3 is a key gene during disulfidptosis","volume":"14","author":"Xu","year":"2023","journal-title":"Front Immunol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2020.07.003","article-title":"EMT, MET, plasticity, and tumor metastasis","volume":"30","author":"Bakir","year":"2020","journal-title":"Trends Cell Biol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-021-00245-6","article-title":"Hepatocellular carcinoma","volume":"7","author":"Llovet","year":"2021","journal-title":"Nat Rev Dis Primers"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.11.018","article-title":"BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update","volume":"76","author":"Reig","year":"2022","journal-title":"J Hepatol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01200-4","article-title":"Hepatocellular carcinoma","volume":"400","author":"Vogel","year":"2022","journal-title":"Lancet"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2022.114684","article-title":"A chemical perspective on the modulation of TEAD transcriptional activities: Recent progress, challenges, and opportunities","volume":"243","author":"Lou","year":"2022","journal-title":"Eur J Med Chem"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3390\/cells8060600","article-title":"Regulation of TEAD transcription factors in cancer biology","volume":"8","author":"Huh","year":"2019","journal-title":"Cells"},{"key":"B27","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1007\/s00018-020-03579-8","article-title":"An overview of signaling pathways regulating YAP\/TAZ activity","volume":"78","author":"Heng","year":"2021","journal-title":"Cell Mol Life Sci"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-0674","article-title":"lncRNA THAP9-AS1 Promotes Pancreatic Ductal Adenocarcinoma Growth and Leads to a Poor Clinical Outcome via Sponging miR-484 and Interacting with YAP","volume":"26","author":"Li","year":"2020","journal-title":"Clin Cancer Res"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac1063","article-title":"TEAD1 regulates cell proliferation through a pocket-independent transcription repression mechanism","volume":"50","author":"Li","year":"2022","journal-title":"Nucleic Acids Res"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202305547","article-title":"Dampened regulatory circuitry of TEAD1\/ITGA1\/ITGA2 promotes TGF\u03b21 signaling to orchestrate prostate cancer progression","volume":"11","author":"Cruz","year":"2024","journal-title":"Adv Sci"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1039260","article-title":"The role of innate immune cells in the tumor microenvironment and research progress in anti-tumor therapy","volume":"13","author":"Lu","year":"2023","journal-title":"Front Immunol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1186\/s12935-024-03335-z","article-title":"Unravelling immune microenvironment features underlying tumor progression in the single-cell era","volume":"24","author":"Du","year":"2024","journal-title":"Cancer Cell Int"},{"key":"B33","doi-asserted-by":"publisher","first-page":"dev196675","DOI":"10.1242\/dev.196675","article-title":"TEAD family transcription factors in development and disease","volume":"148","author":"Currey","year":"2021","journal-title":"Development"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2017.09.003","article-title":"Regulation of the hippo pathway transcription factor TEAD","volume":"42","author":"Lin","year":"2017","journal-title":"Trends Biochem Sci"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90088-g","article-title":"Cloning, expression, and transcriptional properties of the human enhancer factor TEF-1","volume":"65","author":"Xiao","year":"1991","journal-title":"Cell"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20041434","article-title":"The transcriptional co-activator TAZ interacts differentially with transcriptional enhancer factor-1 (TEF-1) family members","volume":"388","author":"Mahoney","year":"2005","journal-title":"Biochem J"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2013.05.029","article-title":"SOX2 regulates YAP1 to maintain stemness and determine cell fate in the osteo-adipo lineage","volume":"3","author":"Seo","year":"2013","journal-title":"Cell Rep"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M900843200","article-title":"TEAD transcription factors mediate the function of TAZ in cell growth and epithelial-mesenchymal transition","volume":"284","author":"Zhang","year":"2009","journal-title":"J Biol Chem"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1664408","article-title":"TEAD mediates YAP-dependent gene induction and growth control","volume":"22","author":"Zhao","year":"2008","journal-title":"Gene Dev"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0605579103","article-title":"Transforming properties of YAP, a candidate oncogene on the chromosome 11q22 amplicon","volume":"103","author":"Overholtzer","year":"2006","journal-title":"Proc Natl Acad Sci USA"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01874-07","article-title":"TAZ promotes cell proliferation and epithelial-mesenchymal transition and is inhibited by the hippo pathway","volume":"28","author":"Lei","year":"2008","journal-title":"Mol Cell Biol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1212021109","article-title":"The Hippo pathway target, YAP, promotes metastasis through its TEAD-interaction domain","volume":"109","author":"Lamar","year":"2012","journal-title":"Proc Natl Acad Sci USA"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2021.12.005","article-title":"Network-based prioritization of cancer biomarkers by phenotype-driven module detection and ranking","volume":"20","author":"Shang","year":"2021","journal-title":"Comput Struct Biotechnol J"},{"key":"B44","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1186\/s12935-024-03306-4","article-title":"Identification of fatty acids synthesis and metabolism-related gene signature and prediction of prognostic model in hepatocellular carcinoma","volume":"24","author":"Zhengdong","year":"2024","journal-title":"Cancer Cell Int"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1481331","article-title":"Signature of immune-related metabolic genes predicts the prognosis of hepatocellular carcinoma","volume":"15","author":"Zhuo","year":"2024","journal-title":"Front Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1567969\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T10:13:52Z","timestamp":1749118432000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1567969\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,5]]},"references-count":45,"alternative-id":["10.3389\/fimmu.2025.1567969"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1567969","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,5]]},"article-number":"1567969"}}