{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T16:48:25Z","timestamp":1785775705441,"version":"3.56.0"},"reference-count":24,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81972653"],"award-info":[{"award-number":["81972653"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Pancreatic adenocarcinoma (PAAD) is a highly aggressive malignancy characterized by rapid progression. In this study, we identify the small MAF protein, MAFF, as a critical driver of PAAD tumorigenesis and a negative regulator of the necroptotic pathway. MAFF silencing significantly suppressed malignant phenotypes in PAAD cells in\u00a0vitro and attenuated overall tumor growth in\u00a0vivo, while ectopic expression promoted tumor progression. Mechanistically, RNA\u2010sequencing and Gene Set Enrichment Analysis (GSEA) identified necroptosis as a key pathway suppressed by MAFF. We established that MAFF acts as a direct transcriptional repressor of\n                    <jats:italic>GATA4<\/jats:italic>\n                    , which in turn serves as a transcriptional activator of the necroptotic executioner\n                    <jats:italic>MLKL<\/jats:italic>\n                    . Consequently, MAFF depletion leads to the reactivation of the GATA4\u2010MLKL axis, triggering necroptotic cell death. The growth\u2010inhibitory effects of MAFF silencing were effectively reversed by pharmacological inhibition of necroptosis or genetic knockdown of\n                    <jats:italic>GATA4<\/jats:italic>\n                    or\n                    <jats:italic>MLKL<\/jats:italic>\n                    . Analysis of clinical data from TCGA and GTEx databases revealed that MAFF is significantly overexpressed in human PAAD tissues compared to normal controls, with elevated levels correlating with advanced histological grade and poor patient prognosis. Collectively, our findings demonstrate that MAFF facilitates PAAD progression by suppressing GATA4\u2010mediated necroptosis, highlighting the MAFF\u2010GATA4\u2010MLKL axis as a promising therapeutic target and prognostic biomarker in pancreatic cancer.\n                  <\/jats:p>","DOI":"10.1111\/cas.70414","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:27:08Z","timestamp":1779193628000},"page":"2181-2193","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>MAFF<\/scp>\n                    Suppresses Necroptosis in Pancreatic Cancer via the\n                    <scp>GATA4<\/scp>\n                    \u2010\n                    <scp>MLKL<\/scp>\n                    Axis"],"prefix":"10.1111","volume":"117","author":[{"given":"Xinwei","family":"Zhou","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory of Brain Disease and Bioinformation, School of Basic Medical Sciences Xuzhou Medical University  Xuzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Brain Disease and Bioinformation, School of Basic Medical Sciences Xuzhou Medical University  Xuzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Sun","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Brain Disease and Bioinformation, School of Basic Medical Sciences Xuzhou Medical University  Xuzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daoyong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Brain Disease and Bioinformation, School of Basic Medical Sciences Xuzhou Medical University  Xuzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.2676"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsb771"},{"key":"e_1_2_12_4_1","first-page":"22550","article-title":"The Therapeutic Value of XL388 in Human Glioma Cells","volume":"12","author":"Zhong 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