Complement Component 3 Is Regulated by TWIST1 and Mediates Epithelial-Mesenchymal Transition

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 C...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2016-02, Vol.196 (3), p.1412-1418
Main Authors: Cho, Min Soon, Rupaimoole, Rajesha, Choi, Hyun-Jin, Noh, Kyunghee, Chen, Jichao, Hu, Qianghua, Sood, Anil K, Afshar-Kharghan, Vahid
Format: Article
Language:English
Subjects:
Animals
Blotting, Western
Cell Line, Tumor
Chromatin Immunoprecipitation
Complement C3 - biosynthesis
Complement C3 - genetics
Epithelial-Mesenchymal Transition - physiology
Female
Gene Expression Regulation, Neoplastic - physiology
Humans
Immunohistochemistry
Mice
Mutagenesis, Site-Directed
Neoplasms - genetics
Neoplasms - metabolism
Neoplasms - pathology
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Real-Time Polymerase Chain Reaction
RNA, Small Interfering
Transfection
Twist-Related Protein 1 - genetics
Twist-Related Protein 1 - metabolism
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1501886