SOX2 Promotes the Epithelial to Mesenchymal Transition of Esophageal Squamous Cells by Modulating Slug Expression through the Activation of STAT3/HIF-α Signaling.
SOX2 Promotes the Epithelial to Mesenchymal Transition of Esophageal Squamous Cells by Modulating Slug Expression through the Activation of STAT3/HIF-α Signaling.
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DOI：
10.3390/ijms160921643
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发表时间：
2015-09-08
影响因子：
5.6
通讯作者：
Wang C
中科院分区：
文献类型：
--
作者：
Gao H;Teng C;Huang W;Peng J;Wang C
转录因子性别决定区（Y SRY）-框2（SOX 2）在维持未分化的胚胎干细胞和神经干细胞的自我更新或多能性中起关键作用。SOX 2的高表达与食管鳞状细胞癌（ESCC）的不良预后相关。我们试图研究SOX 2调节ESCC转移的机制。将SOX 2编码DNA序列插入到pCMV载体中并稳定转染ESCC细胞（Eca-109）。评估SOX 2过表达对细胞迁移、侵袭和上皮向间质转化（EMT）的影响。我们还测量了Slug的表达，以探讨该转录因子是否参与了SOX 2介导的细胞迁移/侵袭和EMT的调节。此外，我们确定了STAT 3/HIF-1α的作用，以进一步探讨SOX 2介导的Slug转移机制。我们的结果表明，SOX 2过表达Eca-109细胞表现出增强的细胞迁移/侵袭。此外，这些细胞表现出EMT特征，即，上皮细胞标记物的表达显著抑制，同时间充质细胞标记物的表达增强。在SOX 2过表达细胞中Slug表达的增加表明该转录因子参与SOX 2调节的转移。而STAT 3/HIF-1α的表达在SOX 2表达细胞中被发现上调，这些转录因子的阻断导致Slug表达在蛋白和mRNA水平上的抑制。结论：这些结果表明，SOX 2至少部分通过激活STAT 3/HIF-1α信号通路调节Slug的表达而促进ESCC的转移。
The transcription factor sex determining region (Y SRY)-box 2 (SOX2) is known to play a crucial role in the maintenance of self renewal or pluripotency of undifferentiated embryonic and neuronal stem cells. An elevated expression of SOX2 has been correlated with poor prognosis of esophageal squamous cell carcinoma (ESCC). We sought to investigate the mechanism(s) by which SOX2 modulates the ESCC metastasis. The SOX2 coding DNA sequence was inserted into pCMV vector and stably transfected in ESCC cells (Eca-109). The effect of SOX2 over expression was evaluated on cell migration, invasion and epithelial to mesenchymal transition (EMT). We also measured the expression of Slug to explore if this transcription factor is involved in SOX2-mediated regulation of cell migration/invasion and EMT. In addition, we determined the role of STAT3/HIF-1α to further probe the mechanism of SOX2-mediated metastasis via Slug. Our results demonstrated that SOX2 over expressing Eca-109 cells showed an enhanced cell migration/invasion. Moreover, these cells exhibited the EMT characteristics, that is, a significantly suppressed expression of the epithelial cells marker with a concomitant enhancement of those of the mesenchymal markers. An increased expression of Slug in SOX2 over expressing cells suggested the involvement of this transcription factor in SOX2-regulated metastasis. Whereas the expressions of STAT3/HIF-1α were found to be up-regulated in SOX2 expressing cells, blockade of these transcription factors resulted in the inhibition of Slug expression at both protein and mRNA levels. Conclusion: These results suggest that SOX2 promoted the metastasis of ESCC, at least in part, by modulating Slug expression through the activation of STAT3/HIF-1α signaling.