Cho Min Soon, Rupaimoole Rajesha, Choi Hyun-Jin, Noh Kyunghee, Chen Jichao, Hu Qianghua, Sood Anil K, Afshar-Kharghan Vahid
Section of Benign Hematology, University of Texas MD Anderson Cancer Center, Houston, TX 77030;
Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030;
J Immunol. 2016 Feb 1;196(3):1412-8. doi: 10.4049/jimmunol.1501886. Epub 2015 Dec 30.
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 twist basic helix-loop-helix transcription factor 1 (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 dependent. We investigated the association between TWIST1 and C3 in malignant tumors and in murine embryos. TWIST1 and C3 colocalized 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.
我们之前已经表明，补体成分3（C3）由恶性上皮细胞分泌。为了解肿瘤细胞中C3表达上调的机制，我们研究了C3启动子，并确定 Twist 碱性螺旋-环-螺旋转录因子1（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（EMT），我们研究了C3对EMT的影响，发现C3降低了癌细胞上E-钙黏蛋白的表达并促进了EMT。我们表明，C3诱导的卵巢癌细胞中E-钙黏蛋白表达的降低是由C3a介导的，并且依赖于Krüppel样因子5。我们研究了TWIST1与C3在恶性肿瘤和小鼠胚胎中的关联。TWIST1和C3在侵袭性肿瘤边缘以及小鼠胚胎的神经嵴和肢芽中共定位。我们的结果确定TWIST1是一种在病理和生理EMT过程中调节C3表达的转录因子。
