{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T02:21:38Z","timestamp":1790043698509,"version":"4.0.1"},"reference-count":28,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Gastric cancer (GC) is a highly prevalent and lethal malignancy. This study aims to investigate the role of Growth Differentiation Factor 15 (GDF15) in regulating ferroptosis through the p62\/Keap1\/Nrf2 pathway and to elucidate its impact on GC progression. GDF15 levels were assessed via Western blot (WB) analysis in both human gastric mucosal cells and GC cell lines. Cellular viability and growth were evaluated using CCK\u20108 assays and colony formation experiments. Cell migration and invasion capabilities were assessed using wound healing and Transwell assays. Levels of ROS, MDA, GSH, GPX4, and Fe\u00b2\u207a in cells were measured using assay kits. JC\u20101 method was utilized for evaluating mitochondrial membrane potential. Tumor weight changes were recorded in BALB\/c nude mouse models. GDF15 was highly expressed in GC cells, and sh\u2010GDF15 inhibited the growth and metastasis of GC cells, increased the expression of ROS and MDA in cells, promoted cell ferroptosis, and inhibited the p62\/Keap1\/Nrf2 pathway in cells (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Compared to the sh\u2010GDF15 group, treatment with the Nrf2 activator, NK\u2010252 reduced ROS and MDA levels, suppressed ferroptosis, and enhanced the activation of the p62\/Keap1\/Nrf2 signaling pathway in GC cells. In GC tissues, the sh\u2010GDF15 group showed reduced tumor volume and weight, elevated Keap1, ROS, and MDA expression, decreased p62 and Nrf2 levels, and increased ferroptosis, which were reversed by the addition of NK\u2010252 (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Conclusively, silencing GDF15 inhibits the p62\/Keap1\/Nrf2 pathway, promoting ferroptosis and suppressing GC progression.<\/jats:p>","DOI":"10.1002\/mc.70037","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T10:22:17Z","timestamp":1755771737000},"page":"1885-1898","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["GDF15\u2010Mediated Regulation of Ferroptosis: Unraveling the p62\/Keap1\/Nrf2 Pathway in Gastric Cancer Development"],"prefix":"10.1002","volume":"64","author":[{"given":"Lixia","family":"Yang","sequence":"first","affiliation":[{"name":"Hunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Changsha Medical University Changsha Hunan China"},{"name":"School of Nursing Changsha Medical University Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Science and Education Guiyang First People\u2032s Hospital Chenzhou Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Yang","sequence":"additional","affiliation":[{"name":"Personnel Department Changsha Medical University Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Dong","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Changsha Medical University Changsha Hunan China"},{"name":"School of Nursing Changsha Medical University Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqiong","family":"Li","sequence":"additional","affiliation":[{"name":"School of Nursing Changsha Medical University Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youhua","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of Changsha Medical University Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,21]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2019.07.045"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-020-09925-3"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.32074\/1591-951X-166"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.21873\/invivo.13009"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-04227-0"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113631"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/6352876"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-022-00939-8"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.76618"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2021.01.007"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2021.11.002"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11081159"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.21765"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.905115"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21114012"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2022.03.022"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-023-03371-y"},{"issue":"7","key":"e_1_2_12_19_1","first-page":"8136","article-title":"Downregulation of Growth Differentiation Factor\u201015 in Trichostatin A\u2010Induced Apoptosis Could Play a Role in Progression of Gastric Cancer","volume":"8","author":"Li Y. L.","year":"2015","journal-title":"International Journal of Clinical and Experimental Pathology"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.46261"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20210518"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2019.04.002"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11658-022-00383-z"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/8973509"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24032925"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.1661"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-024-05089-8"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.120111"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28251"}],"container-title":["Molecular Carcinogenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mc.70037","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T19:20:47Z","timestamp":1760815247000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mc.70037"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,21]]},"references-count":28,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/mc.70037"],"URL":"https:\/\/doi.org\/10.1002\/mc.70037","archive":["Portico"],"relation":{},"ISSN":["0899-1987","1098-2744"],"issn-type":[{"value":"0899-1987","type":"print"},{"value":"1098-2744","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,21]]},"assertion":[{"value":"2025-05-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}