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Preferentially expressed antigen of melanoma (PRAME), a cancer\u2010testis antigen, displays context\u2010dependent functions across malignancies, but its biological role in LUAD metastasis has not been clearly defined. Here, we demonstrate that the significantly upregulated PRAME in metastatic LUAD directly interacts with the m\n                    <jats:sup>6<\/jats:sup>\n                    A methyltransferase METTL3 and promotes its K63\u2010linked non\u2010proteolytic ubiquitination. This modification occurs at lysine 235 of METTL3, increases its protein stability and facilitates METTL3 interaction with METTL14 and WTAP. Consequently, m\n                    <jats:sup>6<\/jats:sup>\n                    A modification of\n                    <jats:italic>TGFB2<\/jats:italic>\n                    mRNA and activation of the TGF\u2010\u03b2 signaling pathway are enhanced, which is essential for PRAME\u2010driven pro\u2010metastatic effects both in vitro and in vivo. Clinically, PRAME expression positively correlates with METTL3 protein abundance and TGF\u2010\u03b2 pathway activation, and is robustly associated with poor clinical outcomes. Taken together, our findings identify K63\u2010linked ubiquitination as a previously unrecognized post\u2010translational modification of METTL3 and underscore the importance of the PRAME\/METTL3\/TGF\u2010\u03b2 axis in LUAD metastasis, providing mechanistic insights and potential therapeutic targets for this malignancy.\n                  <\/jats:p>","DOI":"10.1002\/mco2.71066","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T17:02:10Z","timestamp":1792429330000},"source":"Crossref","is-referenced-by-count":0,"title":["PRAME Augments K63\u2010Linked Ubiquitination and Stabilization of METTL3 to Promote Lung Adenocarcinoma Metastasis"],"prefix":"10.1002","volume":"7","author":[{"given":"Xia","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Institute of Precise Medicine, The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou Guangdong China"},{"name":"Zhongshan School of Medicine Sun 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