{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:07:28Z","timestamp":1785434848725,"version":"3.56.0"},"reference-count":45,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T00:00:00Z","timestamp":1780704000000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2024A1515013057"],"award-info":[{"award-number":["2024A1515013057"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2022A1515111203"],"award-info":[{"award-number":["2022A1515111203"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2024A1515012899"],"award-info":[{"award-number":["2024A1515012899"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32170617"],"award-info":[{"award-number":["32170617"]}],"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":["32370649"],"award-info":[{"award-number":["32370649"]}],"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":["82302078"],"award-info":[{"award-number":["82302078"]}],"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":["81902831"],"award-info":[{"award-number":["81902831"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2703303"],"award-info":[{"award-number":["2022YFC2703303"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Skin cutaneous melanoma (SKCM) continues to pose significant therapeutic challenges owing to its aggressive nature and evolving resistance mechanisms. This study investigates the under\u2010characterized role of Hippo pathway effector TEAD4 in SKCM pathogenesis through integrated multiomics analysis of clinical cohorts (TCGA, GEO, immunotherapy cohorts) combined with functional validation in A375 cell models and xenograft systems. Our pan\u2010cancer analysis identified TEAD4 overexpression as a strong prognostic indicator associated with poor survival and a potential association with inferior immunotherapy response. Functional experiments in A375 cells and xenograft models showed that TEAD4 knockdown impaired proliferation, migration and tumour growth while increasing necroptosis\u2010related markers. Mechanistic investigation showed that TEAD4 directly binds the COL1A2 promoter and promotes its transcription. In A375 cells, COL1A2 overexpression attenuated TEAD4 knockdown\u2010induced changes in AKT\/mTOR signalling, necroptosis\u2010related markers and malignant phenotypes. These findings support a TEAD4 and COL1A2 regulatory model associated with SKCM progression, AKT\/mTOR pathway activity and necroptosis\u2010related phenotypes, and suggest TEAD4 as a prognostic factor and potential biomarker associated with immunotherapy outcome that requires further validation.<\/jats:p>","DOI":"10.1111\/exd.70288","type":"journal-article","created":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T07:35:37Z","timestamp":1780731337000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>TEAD<\/scp>\n                    4 Drives\n                    <scp>SKCM<\/scp>\n                    Progression Through\n                    <scp>COL<\/scp>\n                    1\n                    <scp>A<\/scp>\n                    2 Transcriptional Activation and Modulation of\n                    <scp>AKT<\/scp>\n                    \/m\n                    <scp>TOR<\/scp>\n                    Signalling and Necroptosis\u2010Related Phenotypes"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7094-159X","authenticated-orcid":false,"given":"Jiaqiong","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Zhujiang Hospital Southern Medical University  Guangzhou Guangdong China"},{"name":"Dongguan Maternal and Child Health Care Hospital Postdoctoral Innovation Practice Base of Southern Medical University  Dongguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingchun","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center Guangzhou Medical University  Guangzhou Guangdong China"},{"name":"Department of Medical Genetics\/Experimental Education\/Administration Center, School of Basic Medical Sciences Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongrui","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics\/Experimental Education\/Administration Center, School of Basic Medical Sciences Southern Medical University  Guangzhou China"},{"name":"Gaozhou People's Hospital  Gaozhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Liu","sequence":"additional","affiliation":[{"name":"The First Clinical Medical School of Nanfang Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangkeng","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Zhujiang Hospital Southern Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9319-9925","authenticated-orcid":false,"given":"Fei","family":"He","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics\/Experimental Education\/Administration Center, School of Basic Medical Sciences Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyong","family":"Li","sequence":"additional","affiliation":[{"name":"General Surgery Department, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology The Third Affiliated Hospital, Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2428-6165","authenticated-orcid":false,"given":"Fu","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics\/Experimental Education\/Administration Center, School of Basic Medical Sciences Southern Medical University  Guangzhou China"},{"name":"Department of Fetal Medicine and Prenatal Diagnosis, Zhujiang Hospital Southern Medical University  Guangzhou China"},{"name":"Key Laboratory of Reproductive Health Diseases Research and Translation (Hainan Medical University) Ministry of Education  Haikou Hainan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,6]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045\u2010021\u201001213\u2010z"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2015.3"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.2147\/itt.s134842"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201032674\u20106"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943\u2010019\u20101104\u20101"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2020.165921"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2015.342"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.can\u201019\u20100012"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046\u2010019\u20101346\u20101"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29429"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046\u2010022\u201002377\u20103"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1515\/biol\u20102021\u20100039"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420\u2010022\u201000842\u20108"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2014.10"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deac138"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2020.05.034"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326\u20106066.cir\u201018\u20100436"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2021.01.010"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2023.189050"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2025.118299"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423\u2010020\u201000630\u20103"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/2162402x.2017.1299302"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.4149\/neo_2015_071"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2016.06.002"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.can\u201008\u20104079"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20082044"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.240"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010021\u201000828\u20105"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.05.003"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010022\u201004652\u20109"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12131768"},{"key":"e_1_2_14_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12012\u2010023\u201009789\u20103"},{"key":"e_1_2_14_35_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.82177"},{"key":"e_1_2_14_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13577\u2010023\u201000908\u20104"},{"key":"e_1_2_14_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2023.103012"},{"key":"e_1_2_14_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41417\u2010022\u201000586\u20108"},{"key":"e_1_2_14_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbin.11654"},{"key":"e_1_2_14_40_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.25542"},{"key":"e_1_2_14_41_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.74924"},{"key":"e_1_2_14_42_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2018.1484734"},{"key":"e_1_2_14_43_1","doi-asserted-by":"publisher","DOI":"10.3171\/2022.6.jns22319"},{"key":"e_1_2_14_44_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.220046"},{"key":"e_1_2_14_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21637"},{"key":"e_1_2_14_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40779\u2010025\u201000595\u20102"}],"container-title":["Experimental Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/exd.70288","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/exd.70288","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/exd.70288","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:52:04Z","timestamp":1785433924000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/exd.70288"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":45,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1111\/exd.70288"],"URL":"https:\/\/doi.org\/10.1111\/exd.70288","archive":["Portico"],"relation":{},"ISSN":["0906-6705","1600-0625"],"issn-type":[{"value":"0906-6705","type":"print"},{"value":"1600-0625","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"2025-04-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70288"}}