Interleukin-6-induced epithelial-mesenchymal transition through signal transducer and activator of transcription 3 in human cervical carcinoma
Interleukin-6-induced epithelial-mesenchymal transition through signal transducer and activator of transcription 3 in human cervical carcinoma
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DOI：
10.3892/ijo.2014.2422
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发表时间：
2014-07-01
影响因子：
5.2
通讯作者：
Huang, Jie
中科院分区：
文献类型：
--
作者：
Miao, Jin-Wei;Liu, Li-Jiang;Huang, Jie
上皮间质转化（EMT）是宫颈癌侵袭转移的重要过程。促炎细胞因子白细胞介素-6（IL-6）已被证明是多种癌症中的EMT诱导剂。然而，IL-6是否可以诱导EMT程序以及IL-6诱导人宫颈癌EMT的机制仍有待确定。在本研究中，我们发现，IL-6受体（IL-6 R）和信号转导和转录激活因子3（Stat 3）在人宫颈鳞状细胞癌（CSCC）组织中的高表达，和EMT标志物的表达逆转高分化和低分化的人CSCC。另外的实验表明，宫颈癌细胞系中的IL-6暴露诱导IL-6 R和Stat 3表达，显著促进细胞生长，并改变细胞形态。用IL-6处理宫颈癌细胞系导致E-Cadherin的下调和波形蛋白的上调。重要的是，Stat 3的敲低显著逆转了IL-6诱导的EMT程序，表明Stat 3是IL-6诱导的EMT在人宫颈癌的进展中所必需的。此外，观察到Snail家族EMT调节因子的成员Slug与Stat 3的表达相关。结论IL-6通过Stat 3在EMT诱导中发挥重要作用，有望成为宫颈癌潜在的治疗靶点和生物标志物。
Epithelial-mesenchymal transition (EMT) is an important process in the invasion and metastasis of human cervical carcinoma. The pro-inflammatory cytokine interleukin-6 (IL-6) has been shown as an EMT inducer in multiple carcinomas. However, whether the EMT program can be induced by IL-6 and the mechanisms underlying the IL-6-induced EMT in human cervical carcinoma remain to be determined. In this study, we show that IL-6 receptor (IL-6R) and signal transducer and activator of transcription 3 (Stat3) were highly expressed in human cervical squamous cell carcinoma (CSCC) tissues, and the expression of EMT markers was reversed in well-differentiated and poorly-differentiated human CSCC. Additional experiments showed that IL-6 exposure in cervical carcinoma cell lines induced IL-6R and Stat3 expression, markedly promoted cell growth, and altered cell morphology. The treatment of cervical carcinoma cell lines with IL-6 resulted in down-regulation of E-Cadherin and upregulation of Vimentin. Importantly, knockdown of Stat3 significantly reversed the IL-6-induced EMT program, suggesting that Stat3 is necessary for IL-6-induced EMT in the progression of human cervical carcinoma. Moreover, Slug, a member of the Snail family of EMT regulators, was observed to be associated with the expression of Stat3. We concluded that IL-6 plays an important role through Stat3 in the EMT induction and can be a potential therapeutic target and biomarker for human cervical carcinoma.