Beta1,4-galactosyltransferase V regulates self-renewal of glioma-initiating cell.

Beta1,4-galactosyltransferase V regulates self-renewal of glioma-initiating cell.
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Beta1,4-半乳糖基转移酶 V 调节神经胶质瘤起始细胞的自我更新。

DOI:
10.1016/j.bbrc.2010.04.110
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发表时间:
2010-06
影响因子:
3.1
通讯作者:
Wei Y, Zhou F, Ge Y, Chen H, Cui C, Li Q, Liu D,
Wei Y, Zhou F, Ge Y, Chen H, Cui C, Li Q, Liu D,
中科院分区:
生物学4区
文献类型:
--
作者:
Wei Y, Zhou F, Ge Y, Chen H, Cui C, Li Q, Liu D,

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神经胶质瘤是由自我更新的神经胶质瘤起始细胞群的不受调节的扩增引起的。对于维持胶质瘤起始细胞的自我更新至关重要的调节途径在很大程度上仍然未知。细胞表面N-连接寡糖在决定细胞命运中发挥功能性作用,并与胶质瘤恶性程度相关。以前,我们已经报道了β 1,4-半乳糖基转移酶V(β1,4GalT V)有效地半乳糖基化高度支化的N-聚糖的GlcNAcβ1→ 6 Man臂,并且正调节胶质瘤细胞生长。在此,我们发现通过RNA干扰降低胶质瘤细胞中β1,4GalT V的表达减弱了聚乳糖胺的形成,并抑制了体内肿瘤形成的能力。β1,4GalT V下调可使胶质瘤移植瘤中CD 133阳性细胞减少,并抑制胶质瘤起始细胞的自我更新能力和致瘤潜能。这些数据揭示了β1,4GalT V在胶质瘤起始细胞的自我更新和致瘤性中的关键作用,并表明操纵β1,4GalT V表达可能具有治疗恶性胶质瘤的治疗潜力。
Glioma results from unregulated expansion of a self-renewing glioma-initiating cell population. The regulatory pathways which are essential for sustaining the self-renewal of glioma-initiating cells remain largely unknown. Cell surface N-linked oligosaccharides play functional roles in determining cell fate and are associated with glioma malignancy. Previously, we have reported that β1,4-galactosyltransferase V (β1,4GalT V) effectively galactosylates the GlcNAcβ1→6Man arm of the highly branched N-glycans and positively regulates glioma cell growth. Here, we show that decreasing the expression of β1,4GalT V by RNA interference in glioma cells attenuated the formation of polylactosamine and inhibited the ability of tumor formation in vivo. Down-regulation of β1,4GalT V depleted CD133-positive cells in glioma xenograft, and inhibited the self-renewal capacity and the tumorigenic potential of glioma-initiating cells. These data reveal a critical role of β1,4GalT V in the self-renewal and tumorigenicity of glioma-initiating cells, and indicate that manipulating β1,4GalT V expression may have therapeutic potential for the treatment of malignant glioma.
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