3′-Sulfo-Lex Is Important for Regulation of Integrin Subunit αV
| Autor: | Chunyi Zhang, Xing Zhong Wu, Wei Wu, Ping Hu, Xu Chao Zhu, Chengyou Jia, Da Fu |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Protein subunit
Cell Integrin Down-Regulation Lewis X Antigen Oligosaccharides Transfection Biochemistry Downregulation and upregulation Cell Line Tumor medicine Humans RNA Small Interfering Cell Proliferation biology Chemistry Adhesion Integrin alphaV Molecular biology Fibronectin medicine.anatomical_structure biology.protein Vitronectin Sulfotransferases Trisaccharides |
| Zdroj: | Biochemistry. 49:7811-7820 |
| ISSN: | 1520-4995 0006-2960 |
| Popis: | Carbohydrate structures with a 3'-sulfo betaGal linkage, such as 3'-sulfo-Le(x), can be synthesized by Gal:3-O-sulfotransferase-2 (Gal3ST-2) catalysis, but little is known about their roles in many biological processes. To investigate the role of Gal3ST-2 and its product 3'-sulfo-Le(x), we depleted Gal3ST-2 via siRNA and added exogenous Lewis-x trisaccharide 3'-sulfate sodium salt in human SMMC7721 hepatoma cells. After siRNA transfection, a striking morphological change in SMMC7721 hepatoma cells from polygon to shuttle shape and a significant decrease in the level of adhesion to sL-selectin, HUVEC, fibronectin, vitronectin, and fibrinogen were observed. The expression of integrin subunit alphaV was markedly downregulated, and 3'-sulfated subunit alphaV almost disappeared in the transfectants. The level of cell surface integrin alphaVbeta3 was reduced simultaneously, although total subunit beta3 underwent almost no change. After treatment with exogenous Lewis-x 3'-sulfate, cellular integrin subunit alphaV was upregulated and the level of cell surface integrin alphaVbeta3 was elevated. Interestingly, knockdown of Gal3ST-2 expression effectively inhibited cell proliferation, and the result was significantly correlated with the decrease in the levels of ILK, phosphorylated AKT, and ERK. On the other hand, treatment with Lewis-x trisaccharide 3'-sulfate sodium salt greatly upregulated the phosphorylation of AKT and ERK. Our results also indicated that downregulation of Gal3ST-2 via siRNA transfection was associated with the decrease in the level of expression of anti-apoptotic protein, Bcl-2, with a consequent decrease in the ratios for Bcl-2 to Bax. By exposure to Lewis-x trisaccharide 3'-sulfate sodium salt, the apoptotic response of cells was inhibited. Therefore, Gal3ST-2 and its product, 3'-sulfo-Le(x), were involved in regulation of integrin subunit alphaV and might be associated with cancer cell regulation. |
| Databáze: | OpenAIRE |
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