Glutamine synthetase functions as a negative growth regulator in glioma
Glutamine synthetase functions as a negative growth regulator in glioma
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DOI：
10.1007/s11060-013-1168-5
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发表时间：
2013-06
影响因子：
3.9
通讯作者：
Ying Yin;Weifeng Sun;J. Xiang;Lingxiao Deng;Bin Zhang;P. Xie;W. Qiao;Jian Zou;Chunxing Liu
中科院分区：
文献类型：
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作者：
Ying Yin;Weifeng Sun;J. Xiang;Lingxiao Deng;Bin Zhang;P. Xie;W. Qiao;Jian Zou;Chunxing Liu
我们最近的研究表明，谷氨酰胺合成酶（GS）可能不仅作为一种谷氨酸转换酶在胶质细胞，但也可能作为一个调节星形胶质细胞损伤后迁移。在这份报告中，我们发现，GS表达增加培养大鼠C6胶质瘤细胞，经历了长期的连续繁殖。GS在C6胶质瘤细胞中的稳定过表达导致生长停滞和运动抑制;然而GS的稳定敲低导致运动增强。在与细胞聚集，N-钙粘蛋白水平增加，在C6细胞过度表达GS的细胞-细胞接触的网站，并在C6细胞与稳定的GS敲低下降，总N-钙粘蛋白的表达水平保持不变，在这些细胞。此外，在过度表达GS的C6细胞中，p21（一种有效的细胞周期蛋白依赖性激酶抑制剂）的水平增加，而细胞周期蛋白D1的水平降低。我们的进一步研究表明，N-钙粘蛋白介导的细胞间接触与GS诱导的细胞生长停滞和细胞迁移受损有关，这一点可通过中和性抗N-钙粘蛋白单克隆抗体（GC-4 mAb）对GS抑制细胞生长和运动得到证实。总的来说，这些观察结果表明，一个新的机制，生长调节GS involvesN-cadherin介导的细胞-细胞接触。
Our recent study demonstrated that glutamine synthetase (GS) may not only serve as a glutamate-converting enzyme in glial cells, but may also function as a regulator of astrocyte migration after injury. In this report, we showed that GS expression increased in cultured rat C6 glioma cells that underwent long-term serially propagation. The stable overexpression of GS in C6 glioma cells resulted in growth arrest and motility suppression; however the stable knockdown of GS resulted in motility enhancement. In correlation with cell aggregation,N-cadherin levels increased at sites of cell–cell contact in C6 cells overexpressing GS, and decreased in C6 cells with stable GS knockdown; totalN-cadherin expression levels remained unchanged in these cells. In addition, levels of p21, a potent cyclin-dependent kinase inhibitor, increased, while cyclin D1 levels decreased in C6 cells overexpressing GS. Our additional studies showed thatN-cadherin-mediated cell–cell contacts were implicated in GS-induced cell growth arrest and impairment of cell migration, as evidenced by the inhibition of GS on cell growth and motility by the neutralizing anti-N-cadherin monoclonal antibody (GC-4 mAb). Collectively, these observations suggest a novel mechanism of growth regulation by GS that involvesN-cadherin mediated cell–cell contact.