Hugl-1 inhibits glioma cell growth in intracranial model
Hugl-1 inhibits glioma cell growth in intracranial model
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Hugl-1 抑制颅内模型中神经胶质瘤细胞的生长
DOI：
10.1007/s11060-015-1901-3
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发表时间：
2015-10-01
影响因子：
3.9
通讯作者：
Zhou, Xiuping
中科院分区：
文献类型：
--
作者：
Liu, Xuejiao;Lu, Dong;Zhou, Xiuping
果蝇致死（2）巨幼虫（Drosophilalethal（2）giant larvae，lgl）是一种肿瘤抑制因子，可调节果蝇的信号转导。人巨幼虫蛋白1（human giant larvae-1，Hugl-1）是果蝇基因1的一种同源基因，也被报道与人类某些癌症的发生有关。然而，Hugl-1是否与恶性胶质瘤的发病机制相关仍然知之甚少。在目前的工作中，我们研究了Hugl-1在体外和体内对胶质瘤细胞生长的影响。首先，我们发现Hugl-1蛋白在人脑胶质瘤组织中表达降低，提示Hugl-1参与了胶质瘤的进展。不幸的是，稳定或瞬时过表达Hugl-1并不影响体外胶质瘤细胞增殖。另外，Hugl-1过表达对hippo信号通路没有调节作用。有趣的是，Hugl-1的过表达不仅抑制胶质瘤的发生，而且在裸鼠原位模型中显著抑制细胞增殖并促进U251细胞的凋亡。综上所述，本研究提供了Hugl-1在裸鼠颅内模型中抑制胶质瘤细胞生长的证据，提示Hugl-1可能是胶质瘤治疗的潜在肿瘤靶点。
Drosophilalethal (2) giant larvae (lgl) has been reported as a tumor suppressor and could regulate theDrosophilahippo signaling. Human giant larvae-1(Hugl-1), one human homologue ofDrosophilalgl, also has been reported to be involved in the development of some human cancers. However, whether Hugl-1 is associated with the pathogenesis of malignant gliomas remains poorly understood. In the present work, we examined the effect of Hugl-1 on glioma cell growth both in vitro and in vivo. Firstly, we found that Hugl-1 protein levels decreased in the human glioma tissues, suggesting that Hugl-1 is involved in glioma progression. Unfortunately, either stably or transiently over-expressing Hugl-1 did not affect glioma cell proliferation in vitro. In addition, Hugl-1 over-expression did not regulate hippo signaling pathway. Interestingly, over-expression of Hugl-1 not only inhibited gliomagenesis but also markedly inhibited cell proliferation and promoted the apoptosis of U251 cells in an orthotopic model of nude mice. Taken together, this study provides the evidence that Hugl-1 inhibits glioma cell growth in intracranial model of nude mice, suggesting that Hugl-1 might be a potential tumor target for glioma therapy.