{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:45:30Z","timestamp":1792629930754,"version":"4.5.0"},"reference-count":35,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T00:00:00Z","timestamp":1694476800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cuproptosis, a new type of copper\u2010induced cell death, is involved in the antitumor activity and resistance of multiple chemotherapeutic drugs. Our previous study revealed that adrenomedullin (ADM) was engaged in sunitinib resistance in clear cell renal cell carcinoma (ccRCC). However, it has yet to be investigated whether and how ADM regulates sunitinib resistance by cuproptosis. This study found that the ADM expression was elevated in sunitinib\u2010resistant ccRCC tissues and cells. Furthermore, the upregulation of ADM significantly enhanced the chemoresistance of sunitinib compared with their respective control. Moreover, cuproptosis was involved in ADM\u2010regulated sunitinib resistance by inhibiting mammalian ferredoxin 1 (FDX1) expression. Mechanically, the upregulated ADM activates the p38\/MAPK signaling pathway to promote Forkhead box O3 (FOXO3) phosphorylation and its entry into the nucleus. Consequently, the increased FOXO3 in the nucleus inhibited FDX1 transcription and cell cuproptosis, promoting chemoresistance. Collectively, cuproptosis has a critical effector role in ccRCC progress and chemoresistance and thus is a relevant target to eradicate the cell population of sunitinib resistance.<\/jats:p>","DOI":"10.1096\/fj.202300474r","type":"journal-article","created":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T08:32:01Z","timestamp":1694507521000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Adrenomedullin\/\n                    <scp>FOXO3<\/scp>\n                    enhances sunitinib resistance in clear cell renal cell carcinoma by inhibiting\n                    <scp>FDX1<\/scp>\n                    expression and cuproptosis"],"prefix":"10.1096","volume":"37","author":[{"given":"Xin","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Urology The Second Hospital of Hebei Medical University  Shijiazhuang 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