title: Plasminogen activator inhibitor-1 as regulator of tumor-initiating cell properties in head and neck cancers.
abstract: The existence of tumor-initiating cells (TICs) has been described in head and neck cancers. Plasminogen activator inhibitor-1 (PAI-1) has been demonstrated to act as a prognostic factor in head and neck cancers.
  
  
  
  Tiplaxtinin (PAI-039), a specific inhibitor of PAI-1, and PAI-1-specific siRNA were used to examine the role of PAI-1 in the self-renewal property of head and neck cancer-TICs by tumorsphere formation. Western blot, real-time polymerase chain reaction, and luciferase-based reporter assay were used to study the effect of PAI-039 in the sex-determining region Y-box 2 (Sox2) expression.
  
  
  
  PAI-039 suppressed the self-renewal capability of head and neck cancer-TICs derived from head and neck cancer cell lines through the inhibition of Sox2 expression. PAI-039 decreased the activity of the core promoter and the enhancer of the Sox2 gene in head and neck cancer-TICs. Knockdown of PAI-1 expression also inhibited self-renewal and radioresistance properties of head and neck cancer-TICs.
  
  
  
  The inhibition of PAI-1 by PAI-039 or siRNA could suppress head and neck cancer-TICs within head and neck cancer cell lines through the downregulation of Sox2. © 2015 Wiley Periodicals, Inc. Head Neck 38: E895-E904, 2016.
authors.affiliation: Radiation Oncology Department, Chung Shan Medical University Hospital, Taichung City, Taiwan.|Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Yueh-Chun
authors.initials: YC
authors.lastname: Lee
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung, Taiwan.|Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.|Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Cheng-Chia
authors.initials: CC
authors.lastname: Yu
authors.affiliation: School of Biomedical Sciences, Chung Shan Medical University, Taichung City, Taiwan.
authors.forename: Chih
authors.initials: C
authors.lastname: Lan
authors.affiliation: Graduate Institute of Basic Medical Science, School of Medicine, China Medical University, Taichung, Taiwan.|Department of Microbiology, School of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Che-Hsin
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Institute of Anatomy and Cell Biology, School of Medicine, National Yang Ming University, Taipei, Taiwan.
authors.forename: Hsueh-Te
authors.initials: HT
authors.lastname: Lee
authors.affiliation: Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan.|School of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Yu-Liang
authors.initials: YL
authors.lastname: Kuo
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.|Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung, Taiwan.|School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Po-Hui
authors.initials: PH
authors.lastname: Wang
authors.affiliation: School of Biomedical Sciences, Chung Shan Medical University, Taichung City, Taiwan.|Department of Medical Research, Chung Shan Medical University Hospital, Taichung City, Taiwan.
authors.forename: Wen-Wei
authors.initials: WW
authors.lastname: Chang
mesh_terms: D045744:Cell Line, Tumor; D004742:Enhancer Elements, Genetic; D055785:Gene Knockdown Techniques; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007210:Indoleacetic Acids / Q000494:pharmacology; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors / Q000378:metabolism*
chemical_list: D007210:Indoleacetic Acids; D017395:Plasminogen Activator Inhibitor 1; D034741:RNA, Small Interfering; C051321:SERPINE1 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; C488103:tiplaxtinin
keywords: Sox2; head and neck cancer; plasminogen activator inhibitor-1 (PAI-1); tiplaxtinin (PAI-039); tumor-initiating cells