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- Title
Knockdown of ST6Gal‐I expression in human hepatocellular carcinoma cells inhibits their exosome‐mediated proliferation‐ and migration‐promoting effects.
- Authors
Wang, Liping; Chen, Xixi; Wang, Lingyan; Wang, Shujing; Li, Wenli; Liu, Yubo; Zhang, Jianing
- 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.
- Subjects
HEPATOCELLULAR carcinoma; LIQUID chromatography-mass spectrometry; GLYCOPROTEIN analysis
- Publication
IUBMB Life, 2021, Vol 73, Issue 11, p1378
- ISSN
1521-6543
- Publication type
Article
- DOI
10.1002/iub.2562