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However, the energetic process by which tumour cells produce EVs remains poorly understood. Here, we demonstrate the involvement of <jats:italic>\u03b2<\/jats:italic>\u2010hexosaminidase B (HEXB) in mediating EV release in response to oxidative stress, thereby promoting the development of hepatocellular carcinoma (HCC). Mechanistically, reactive oxygen species (ROS) stimulate the nuclear translocation of transcription factor EB (TFEB), leading to the upregulation of both HEXB and its antisense lncRNA HEXB\u2010AS. HEXB\u2010AS can bind HEXB to form a protein\/RNA complex, which elevates the protein stability of HEXB. The stabilized HEXB interacts with lysosome\u2010associated membrane glycoprotein 1 (LAMP1), disrupting lysosome\u2010multivesicular body (MVB) fusion, which protects EVs from degradation. Knockdown of HEXB efficiently inhibits EV release and curbs HCC growth both in vitro and in vivo. Moreover, targeting HEXB by M\u201031850 significantly inhibits HCC growth, especially when combined with GW4869, an inhibitor of exosome release. Our results underscore the critical role of HEXB as a modulator that promotes EV release during HCC development.<\/jats:p>","DOI":"10.1002\/jev2.12468","type":"journal-article","created":{"date-parts":[[2024,6,30]],"date-time":"2024-06-30T00:14:05Z","timestamp":1719706445000},"source":"Crossref","is-referenced-by-count":37,"title":["Oxidative stress induces extracellular vesicle release by upregulation of HEXB to facilitate tumour growth in experimental hepatocellular carcinoma"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8497-2779","authenticated-orcid":false,"given":"Jiufei","family":"Duan","sequence":"first","affiliation":[{"name":"Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy West China Hospital, and West China School of Basic Medical Sciences &amp; Forensic Medicine Sichuan University Chengdu P.R. 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