Complement Component 3 Is Regulated by TWIST1 and Mediates Epithelial-Mesenchymal Transition.
Complement Component 3 Is Regulated by TWIST1 and Mediates Epithelial-Mesenchymal Transition.
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DOI：
10.4049/jimmunol.1501886
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发表时间：
2016-02-01
期刊：
影响因子：
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通讯作者：
Afshar-Kharghan V
中科院分区：
文献类型：
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作者：
Cho MS;Rupaimoole R;Choi HJ;Noh K;Chen J;Hu Q;Sood AK;Afshar-Kharghan V
我们以前已经表明，补体成分3 （C3）是由恶性上皮细胞分泌的。为了了解C3在肿瘤细胞中表达上调的机制，我们研究了C3启动子；发现TWIST1与C3启动子结合并增强其表达。由于TWIST1介导上皮-间质转化（epithelial-mesenchymal transition， EMT），我们研究了C3对EMT的影响，发现C3可降低E-cadherin在癌细胞上的表达，促进EMT。我们发现c3诱导的卵巢癌细胞中E-cadherin表达的降低是由C3a介导的，并且是kr<s:1> ppel样因子5 （KLF5）依赖性的。我们研究了TWIST1和C3在恶性肿瘤和小鼠胚胎中的关系。TWIST1和C3共定位于侵袭性肿瘤边缘，以及小鼠胚胎的神经嵴和肢体芽。我们的研究结果发现TWIST1是一个转录因子，在病理和生理性EMT中调节C3的表达。
We have previously shown that complement component 3 (C3) is secreted by malignant epithelial cells. To understand the mechanism of upregulation of C3 expression in tumor cells we studied the C3 promoter; and identified that TWIST1 binds to the C3 promoter and enhances its expression. Because TWIST1 mediates epithelial-mesenchymal transition (EMT), we studied the effect of C3 on EMT and found that C3 decreased E-cadherin expression on cancer cells and promoted EMT. We showed that C3-induced reduction in E-cadherin expression in ovarian cancer cells was mediated by C3a and is Krüppel-like factor 5 (KLF5)-dependent. We investigated the association between TWIST1 and C3 in malignant tumors and in murine embryos. TWIST1 and C3 co-localized at the invasive tumor edges, and in the neural crest and limb buds of mouse embryos. Our results identified TWIST1 as a transcription factor that regulates C3 expression during pathologic and physiologic EMT.