Stat3 induces oncogenic Skp2 expression in human cervical carcinoma cells
Stat3 induces oncogenic Skp2 expression in human cervical carcinoma cells
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DOI：
10.1016/j.bbrc.2012.01.004
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发表时间：
2012-02-03
影响因子：
3.1
通讯作者：
Yang, Dan
中科院分区：
文献类型：
--
作者：
Huang, Hanhui;Zhao, Wenrong;Yang, Dan
失调的Skp 2功能促进细胞增殖，这与在许多类型的人类癌症（包括宫颈癌（CC））中Skp 2过表达的观察结果一致。然而，Skp 2表达升高的分子机制尚未完全研究。白细胞介素-6（IL-6）诱导的Stat 3活化被认为是多种肿瘤生长和转移的关键。在这里，我们证明Skp 2是人宫颈癌细胞中Stat 3的直接转录靶点。我们的数据表明，IL-6管理或转染的组成型激活的Stat 3在HeLa细胞激活Skp 2 mRNA转录。利用荧光素酶报告基因和ChIP检测，我们发现Stat 3与Skp 2的启动子区结合，并通过募集P300来促进其活性。由于Skp 2表达的增加，内源性p27蛋白水平显著降低。因此，我们的研究结果表明，以前未知的Stat 3-Skp 2分子网络控制宫颈癌的发展。(C)2012 Elsevier Inc. All rights reserved.
Dysregulated Skp2 function promotes cell proliferation, which is consistent with observations of Skp2 over-expression in many types of human cancers, including cervical carcinoma (CC). However, the molecular mechanisms underlying elevated Skp2 expression have not been fully explored. Interleukin-6 (IL-6) induced Stat3 activation is viewed as crucial for multiple tumor growth and metastasis. Here, we demonstrate that Skp2 is a direct transcriptional target of Stat3 in the human cervical carcinoma cells. Our data show that IL-6 administration or transfection of a constitutively activated Stat3 in HeLa cells activates Skp2 mRNA transcription. Using luciferase reporter and ChIP assays, we show that Stat3 binds to the promoter region of Skp2 and promotes its activity through recruiting P300. As a result of the increase of Skp2 expression, endogenous p27 protein levels are markedly decreased. Thus, our results suggest a previously unknown Stat3-Skp2 molecular network controlling cervical carcinoma development. (C) 2012 Elsevier Inc. All rights reserved.