Abstract
Abnormal sialylation is a distinctive feature of human hepatocellular carcinoma (HCC) and is closely related to its malignant properties. Exosomes have characteristic protein and lipid composition; however, the results concerning glycoprotein composition and glycosylation are scarce. In this study, liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified multiple microvesicle-related sialylated proteins including CD63, a classic marker of exosomes. The silencing of α2,6-sialyltransferase I (ST6Gal-I) significantly reduced the levels of α2,6-sialylated glycoconjugates on CD63 and the surface of HCC-derived exosomes (HCC-exo). And surface glycoconjugates play important roles in exosomes biogenesis and in their interaction with other cells. Compared to exosomes derived from naive HCC cells, α2,6-sialylation degradation abolished both the proliferation-promoting and migration-promoting effects of HCC-exo. Further analysis revealed that the Akt/GSK-3β or JNK1/2 signaling mediates HCC-exo-mediated proliferation in HCC cells, while ST6Gal-I silencing deactivated this pathway. These findings suggest that a loss of α2,6-sialylation decreases HCC progression through the loss of cancer cell-derived exosomes; furthermore, it opens novel perspectives to further explore the functional role of glycans in the biology of exosomes.