CCAAT/enhancer binding protein β induces motility and invasion of glioblastoma cells through transcriptional regulation of the calcium binding protein S100A4.
CCAAT/enhancer binding protein β induces motility and invasion of glioblastoma cells through transcriptional regulation of the calcium binding protein S100A4.
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DOI：
10.18632/oncotarget.2976
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发表时间：
2015-02-28
期刊：
影响因子：
--
通讯作者：
Perez-Castillo A
中科院分区：
文献类型：
--
作者：
Aguilar-Morante D;Morales-Garcia JA;Santos A;Perez-Castillo A
我们之前的研究表明，降低CCAAT/增强子结合蛋白β (C/EBPβ)的表达可抑制胶质母细胞瘤细胞的生长，并降低其转化能力和迁移能力。与此一致，我们发现C/EBPβ缺失降低了参与转移和侵袭的不同基因的mRNA水平。其中，我们发现S100钙结合蛋白A4 （S100A4）在缺乏C/EBPβ的胶质母细胞瘤细胞中几乎检测不到。在这里，我们评估了S100A4在胶质母细胞瘤细胞中C/EBPβ观察到的效应中的可能作用，以及C/EBPβ控制S100A4水平的机制。我们的研究结果表明，C/EBPβ抑制显著降低小鼠GL261和人T98G胶质母细胞瘤细胞中S100A4的水平。通过使用S100A4启动子报告子，我们观察到C/EBPβ显著诱导了S100A4基因的转录激活。此外，在C/ ebp β缺失的胶质母细胞瘤细胞中，S100A4的过表达逆转了该转录因子诱导的增强的迁移和运动。我们的数据还指出S100A4在胶质母细胞瘤细胞侵袭中的作用，并表明C/EBPβ基因通过直接调控S100A4来控制GL261和T98G细胞的侵袭潜力。最后，本研究表明C/EBPβ在GL261胶质母细胞瘤细胞中维持干细胞群的作用。
We have previously shown that decreased expression of CCAAT/Enhancer binding protein β (C/EBPβ) inhibits the growth of glioblastoma cells and diminishes their transformation capacity and migration. In agreement with this, we showed that C/EBPβ depletion decreases the mRNA levels of different genes involved in metastasis and invasion. Among these, we found S100 calcium binding protein A4 (S100A4) to be almost undetectable in glioblastoma cells deficient in C/EBPβ. Here, we have evaluated the possible role of S100A4 in the observed effects of C/EBPβ in glioblastoma cells and the mechanism through which S100A4 levels are controlled by C/EBPβ. Our results show that C/EBPβ suppression significantly reduced the levels of S100A4 in murine GL261 and human T98G glioblastoma cells. By employing an S100A4-promoter reporter, we observed a significant induction in the transcriptional activation of the S100A4 gene by C/EBPβ. Furthermore, overexpression of S100A4 in C/EBPβ-depleted glioblastoma cells reverses the enhanced migration and motility induced by this transcription factor. Our data also point to a role of S100A4 in glioblastoma cell invasion and suggest that the C/EBPβ gene controls the invasive potential of GL261 and T98G cells through direct regulation of S100A4. Finally, this study indicates a role of C/EBPβ on the maintenance of the stem cell population present in GL261 glioblastoma cells.
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影响因子：
11.2
作者：
Harris MA;Yang H;Low BE;Mukherjee J;Guha A;Bronson RT;Shultz LD;Israel MA;Yun K
通讯作者：
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影响因子：
3.7
作者：
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6.2
作者：
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影响因子：
5.3
作者：
HSU, W;KERPPOLA, TK;CHENKIANG, S
通讯作者：
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