Reelin is involved in transforming growth factor-β1-induced cell migration in esophageal carcinoma cells.
Reelin is involved in transforming growth factor-β1-induced cell migration in esophageal carcinoma cells.
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DOI：
10.1371/journal.pone.0031802
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Liu Z
中科院分区：
文献类型：
--
作者：
Yuan Y;Chen H;Ma G;Cao X;Liu Z
Reelin（Reelin，RELN）是一种由发育中的大脑皮层Cajal-Retzius细胞分泌的糖蛋白，在神经元迁移中起重要作用，但其在细胞迁移和肿瘤转移中的作用尚不清楚。在此，我们发现TGF-β1处理后KYSE-510细胞的运动性显著增加。此外，TGF-β1可降低KYSE-30细胞中JNK mRNA的表达，而Reelin的过表达至少部分逆转了TGF-β1诱导的KYSE-30细胞迁移。此外，TGF-β1对KYSE-510细胞中Reelin表达的负调控作用是通过其诱导的转录因子Snail实现的。TGF-β1处理后，Snail诱导ESCC细胞中ESCC启动子活性降低，Snail通过与ESCC启动子区域的E-box序列结合抑制ESCC启动子活性和表达。在KYSE-510细胞中，敲低CD 3 N诱导细胞迁移，以及间充质标志物表达的增加。总之，Reelin是TGF-β1诱导的细胞迁移过程中必不可少的负调节因子，并且通过Snail调节在转录水平上被TGF-β途径抑制。因此，Reelin与TGF-β通路的相关性在肿瘤转移中起重要作用，Reelin可能成为未来临床抗肿瘤转移的靶点之一。
Reelin (RELN), which is a glycoprotein secreted by Cajal-Retzius cells of the developing cerebral cortex, plays an important role in neuronal migration, but its role in cell migration and cancer metastasis is largely unclear. Here, we showed that cell motility was significantly increased in KYSE-510 cells by TGF-β1 treatment. Moreover, TGF-β1 decreased RELN mRNA expression and overexpression of Reelin at least partly reversed TGF-β1-induced cell migration in KYSE-30 cells. Furthermore, this negative regulation of Reelin expression by TGF-β1 was through Snail, one transcription factor which was induced by TGF-β1 in KYSE-510 cells. RELN promoter activity was reduced in parallel with the induction of Snail after TGF-β1 treatment and Snail suppressed both RELN promoter activity and expression through binding to E-box sequences in the RELN promoter region in ESCC cells. Knockdown of RELN induced cell migration in KYSE-510 cells, together with the increase of mesenchymal markers expression. Taken together, Reelin is an essential negative regulator in the TGF-β1-induced cell migration process, and is suppressed by TGF-β pathway at the transcriptional level through Snail regulation. Therefore, the correlation of Reelin and TGF-β pathway was critical in cancer metastasis, and Reelin could be one potential anti-metastasis target in future clinical practice.
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