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Functionally, DIXDC1 enhances BCa cell migration, invasion, proliferation, and lymph node dissemination in vivo. Mechanistically, DIXDC1 directly binds to dihydrolipoamide S\u2010acetyltransferase (DLAT), a key enzyme in the tricarboxylic acid cycle and a central effector of cuproptosis. This interaction impedes ubiquitin\u2010proteasome\u2010mediated degradation of DLAT, thereby stabilizing DLAT protein levels. Through a DLAT\u2010dependent pathway, DIXDC1 further augments the mRNA stability of the oncogenes\n                    <jats:italic>NEK7<\/jats:italic>\n                    and\n                    <jats:italic>CCNE2<\/jats:italic>\n                    , fueling tumor progression. Importantly, DIXDC1 shields BCa cells from copper\u2010induced DLAT oligomerization and confers marked resistance to Elesclomol\u2010Cu (ES\u2010Cu)\u2010triggered cuproptosis. Depletion of DIXDC1 profoundly sensitizes tumors to cuproptosis in vivo. Collectively, our study unveils the DIXDC1\u2010DLAT axis as a pivotal regulator that coordinately drives metastatic progression and suppresses copper\u2010induced cell death, offering a promising therapeutic target for advanced BCa.\n                  <\/jats:p>","DOI":"10.1002\/advs.77435","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T15:47:36Z","timestamp":1787845656000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["DIXDC1 Promotes Lymphatic Metastasis and Resistance to Cuproptosis in Bladder Cancer Through Mediating DLAT"],"prefix":"10.1002","author":[{"given":"Hongqiong","family":"Li","sequence":"first","affiliation":[{"name":"Department of Urology The Second Affiliated Hospital of Kunming Medical University  Kunming Yunnan People's Republic of 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