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Exosomes have characteristic protein and lipid composition; however, the results concerning glycoprotein composition and glycosylation are scarce. In this study, liquid chromatography\u2013tandem mass spectrometry (LC\u2010MS\/MS) identified multiple microvesicle\u2010related sialylated proteins including CD63, a classic marker of exosomes. The silencing of \u03b12,6\u2010sialyltransferase I (ST6Gal\u2010I) significantly reduced the levels of \u03b12,6\u2010sialylated glycoconjugates on CD63 and the surface of HCC\u2010derived exosomes (HCC\u2010exo). And surface glycoconjugates play important roles in exosomes biogenesis and in their interaction with other cells. Compared to exosomes derived from naive HCC cells, \u03b12,6\u2010sialylation degradation abolished both the proliferation\u2010promoting and migration\u2010promoting effects of HCC\u2010exo. Further analysis revealed that the Akt\/GSK\u20103\u03b2 or JNK1\/2 signaling mediates HCC\u2010exo\u2010mediated proliferation in HCC cells, while ST6Gal\u2010I silencing deactivated this pathway. These findings suggest that a loss of \u03b12,6\u2010sialylation decreases HCC progression through the loss of cancer cell\u2010derived exosomes; furthermore, it opens novel perspectives to further explore the functional role of glycans in the biology of exosomes.<\/jats:p>","DOI":"10.1002\/iub.2562","type":"journal-article","created":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T16:40:18Z","timestamp":1632501618000},"page":"1378-1391","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Knockdown of <scp>ST6Gal\u2010I<\/scp> expression in human hepatocellular carcinoma cells inhibits their exosome\u2010mediated proliferation\u2010 and migration\u2010promoting effects"],"prefix":"10.1002","volume":"73","author":[{"given":"Liping","family":"Wang","sequence":"first","affiliation":[{"name":"School of Life and Pharmaceutical Sciences Dalian University of Technology  Panjin 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