title: Sox5 induces epithelial to mesenchymal transition by transactivation of Twist1.
abstract: The epithelial to mesenchymal transition (EMT), a highly conserved cellular program, plays an important role in normal embryogenesis and cancer metastasis. Twist1, a master regulator of embryonic morphogenesis, is overexpressed in breast cancer and contributes to metastasis by promoting EMT. In exploring the mechanism underlying the increased Twist1 in breast cancer cells, we found that the transcription factor SRY (sex-determining region Y)-box 5(Sox5) is up-regulation in breast cancer cells and depletion of Sox5 inhibits breast cancer cell proliferation, migration, and invasion. Furthermore, depletion of Sox5 in breast cancer cells caused a dramatic decrease in Twist1 and chromosome immunoprecipitation assay showed that Sox5 can bind directly to the Twist1 promoter, suggesting that Sox5 transactivates Twist1 expression. We further demonstrated that knockdown of Sox5 up-regulated epithelial phenotype cell biomarker (E-cadherin) and down-regulated mesenchymal phenotype cell biomarkers (N-cadherin, Vimentin, and Fibronectin 1), resulting in suppression of EMT. Our study suggests that Sox5 transactivates Twist1 expression and plays an important role in the regulation of breast cancer progression.
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Department of Pathology, The Basic Medical College of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Xin-Hong
authors.initials: XH
authors.lastname: Pei
authors.affiliation: Department of Pathology, The Basic Medical College of Zhengzhou University, Zhengzhou, Henan, China; Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Xin-Quan
authors.initials: XQ
authors.lastname: Lv
authors.affiliation: Department of Pathology, The Basic Medical College of Zhengzhou University, Zhengzhou, Henan, China; Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. Electronic address: Lihuixiang1955@163.com.
authors.forename: Hui-Xiang
authors.initials: HX
authors.lastname: Li
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D061986:MCF-7 Cells; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000235:genetics*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D055755:SOXD Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014410:Tumor Stem Cell Assay; D051879:Twist-Related Protein 1 / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D009687:Nuclear Proteins; D012334:RNA, Neoplasm; D012261:Ribonucleoproteins; C490301:SOX5 protein, human; D055755:SOXD Transcription Factors; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; C026452:messenger ribonucleoprotein
keywords: Breast cancer; EMT; Sox5; Twist1