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Adv."],"published-print":{"date-parts":[[2026,6,26]]},"abstract":"<jats:p>\n                    RNA modification pathways are often misregulated in various cancers, with\n                    <jats:italic toggle=\"yes\">N<\/jats:italic>\n                    <jats:sup>6<\/jats:sup>\n                    -methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A) having a pivotal role in cancer progression and metastasis. Methyltransferase-like 3 (METTL3), a core component of the m\n                    <jats:sup>6<\/jats:sup>\n                    A methyltransferase complex, not only functions as an m\n                    <jats:sup>6<\/jats:sup>\n                    A writer but also promotes tumorigenesis through m\n                    <jats:sup>6<\/jats:sup>\n                    A-independent mechanisms. Here, we show that METTL3 is mislocalized to the cytoplasm in breast cancer tumors from patients, contributing to the oncogenic phenotype. Cytoplasmic METTL3 interacts with EXOC7, a key regulator of exocytosis, promoting its stabilization. In addition, METTL3 regulates m\n                    <jats:sup>6<\/jats:sup>\n                    A-dependent alternative splicing of\n                    <jats:italic toggle=\"yes\">EXOC7<\/jats:italic>\n                    . Silencing\n                    <jats:italic toggle=\"yes\">METTL3<\/jats:italic>\n                    impairs vesicle trafficking and the breast cancer secretome\u2014effects that do not rely on its enzymatic activity but instead involve METTL3-mediated stabilization of EXOC7 and potentially other exocyst components. Furthermore, METTL3 knockdown impairs invadopodia formation, collagen matrix invasion, and focal adhesion morphology in vitro, while inhibition of METTL3 catalytic activity does not. Our findings uncover noncatalytic roles of METTL3 in regulating exocytosis and the cancer secretome.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adz2434","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T17:59:33Z","timestamp":1782496773000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["METTL3 regulates exocytosis independently of m\n                    <sup>6<\/sup>\n                    A"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8047-9298","authenticated-orcid":true,"given":"Margalida","family":"Esteva-Socias","sequence":"first","affiliation":[{"name":"Department of Molecular Biology, Ume\u00e5 University, Ume\u00e5, Sweden."},{"name":"Wallenberg Centre for Molecular Medicine, Ume\u00e5 University, Ume\u00e5, 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