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We investigated CDDP\u2010resistance mechanisms mediated by extracellular vesicles (EVs) and ATPase copper transporting beta (ATP7B) in HNSCC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We established CDDP\u2010resistant sublines of HNSCC cells and verified their ATP7B expression. We used an EV secretion inhibitor (GW4869) and ATP7B short hairpin (sh)RNA transfection to examine the correlation between EV secretion and ATP7B expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The CDDP\u2010resistant HNSCC sublines showed decreased CDDP sensitivity and increased ATP7B expression. GW4869 suppressed ATP7B expression, and ATP7B shRNA transfection suppressed EV secretion. The suppressions of EV secretion and ATP7B expression both enhanced CDDP's cell\u2010killing effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>EVs were involved in the ATP7B\u2010mediated mechanism underlying CDDP resistance. Further clarification of the EV\u2010induced CDDP\u2010resistance mechanism may lead to novel therapeutic strategies for HNSCC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/hed.27620","type":"journal-article","created":{"date-parts":[[2024,1,2]],"date-time":"2024-01-02T09:06:36Z","timestamp":1704186396000},"page":"636-650","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Novel mechanism of cisplatin resistance in head and neck squamous cell carcinoma involving extracellular vesicles and a copper transporter system"],"prefix":"10.1002","volume":"46","author":[{"given":"Tatsuo","family":"Ogawa","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences Okayama University  Okayama 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