Tumor cell migration and invasion are regulated by expression of variant integrin glycoforms.
Tumor cell migration and invasion are regulated by expression of variant integrin glycoforms.
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DOI：
10.1016/j.yexcr.2008.07.021
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发表时间：
2008-10-01
影响因子：
3.7
通讯作者：
Bellis SL
中科院分区：
文献类型：
--
作者：
Shaikh FM;Seales EC;Clem WC;Hennessy KM;Zhuo Y;Bellis SL
The ST6Gal-I glycosyltransferase, which adds α2-6-linked sialic acids to glycoproteins, is overexpressed in colon adenocarcinoma, and enzyme activity is correlated with tumor cell invasiveness. Previously we reported that forced expression of oncogenic ras in HD3 colonocytes causes upregulation of ST6Gal-I, leading to increased α2-6 sialylation of β1 integrins. To determine whether ras-induced sialylation is involved in promoting the tumor cell phenotype, we used shRNA to downregulate ST6Gal-I in ras-expressors, and then monitored integrin-dependent responses. Here we show that forced ST6Gal-I downregulation, leading to diminished α2-6 sialylation of integrins, inhibits cell adhesion to collagen-I, a β1 ligand. Correspondingly, collagen binding is reduced by enzymatic removal of cell surface sialic acids from ras-expressors with high ST6Gal-I levels (i.e., no shRNA). Cells with forced ST6Gal-I downregulation also exhibit decreased migration on collagen-I and diminished invasion through Matrigel. Importantly, GD25 cells, which lack β1 integrins (and ST6Gal-I), do not demonstrate differential invasiveness when forced to express ST6Gal-I, suggesting that the effects of variant sialylation are mediated specifically by β1 integrins. The observation that cell migration and invasion can be blocked in oncogenic ras-expressing cells by forcing ST6Gal-I downregulation implicates differential sialylation as an important ras effector, and also suggests that ST6Gal-I is a promising therapeutic target.
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影响因子：
3.5
作者：
Böttger, TC;Maschek, H;Junginger, T
通讯作者：
Junginger, T
影响因子：
12.7
作者：
Kaneko, Y;Yamamoto, H;Moskal, JR
通讯作者：
Moskal, JR
影响因子：
11.4
作者：
Damiano, JS;Hazlehurst, LA;Dalton, WS
通讯作者：
Dalton, WS
影响因子：
8
作者：
Aoudjit, F;Vuori, K
通讯作者：
Vuori, K
DOI：
10.1073/pnas.93.9.4454
发表时间：
1996-04-30
影响因子：
11.1
作者：
James, G;Goldstein, JL;Brown, MS
通讯作者：
Brown, MS