title: Complement Component 3 Is Regulated by TWIST1 and Mediates Epithelial-Mesenchymal Transition.
abstract: 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.
authors.affiliation: Section of Benign Hematology, University of Texas MD Anderson Cancer Center, Houston, TX 77030;
authors.forename: Min Soon
authors.identifier: http://orcid.org/0000-0002-9992-8356
authors.initials: MS
authors.lastname: Cho
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030;
authors.forename: Rajesha
authors.initials: R
authors.lastname: Rupaimoole
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030;
authors.forename: Hyun-Jin
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030;
authors.forename: Kyunghee
authors.initials: K
authors.lastname: Noh
authors.affiliation: Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030;
authors.forename: Jichao
authors.identifier: http://orcid.org/0000-0003-2749-8550
authors.initials: J
authors.lastname: Chen
authors.affiliation: Section of Benign Hematology, University of Texas MD Anderson Cancer Center, Houston, TX 77030;
authors.forename: Qianghua
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030; Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030; and Center for RNA Intereference and Non-Coding RNAs, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
authors.affiliation: Section of Benign Hematology, University of Texas MD Anderson Cancer Center, Houston, TX 77030; vakharghan@mdanderson.org.
authors.forename: Vahid
authors.initials: V
authors.lastname: Afshar-Kharghan
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D003176:Complement C3 / Q000096:biosynthesis* / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D016297:Mutagenesis, Site-Directed; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D003176:Complement C3; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1