title: ZEB1 as an indicator of tumor recurrence for areca quid chewing-associated oral squamous cell carcinomas.
abstract: BACKGROUND
  Oral squamous cell carcinoma (OSCC) is the sixth most prevalent malignancy worldwide and the third most common cancer in developing nation. Most OSCC patients relapse within months after receiving treatment. Therefore, searching the biomarkers of recurrence is urgently required to improve OSCC patient survival.
  
  
  METHODS
  We set out to explore whether expression of ZEB1 could be triggered in oral epithelial cells (SG and FaDu) by arecoline in vitro. Control and ZEB1-knockdown arecoline-stimulated SG and FaDu were subjected to migration/invasiveness/anchorage-independent growth assay. Primary and recurrent OSCC tissues from areca quid chewers were analyzed using real-time RT-PCR analysis for ZEB1 expression.
  
  
  RESULTS
  Arecoline led to dose-dependent elevation of ZEB1 expression in SG and FaDu cells. Downregulation of ZEB1 by lentiviral infection significantly reversed arecoline-induced oncogenicity including migration ability, cell invasiveness, and anchorage-independent growth in SG and FaDu cells. Clinically, the level of ZEB1 expression was higher in recurrent OSCC tumor samples but lower in primary lesions.
  
  
  CONCLUSIONS
  Targeting ZEB1 might offer a new strategy for the treatment of OSCC patients. ZEB1 can serve as a progression and relapse marker in OSCC patients.
authors.affiliation: Department of Oral Maxillofacial Surgery, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan.
authors.forename: Cho Ming
authors.initials: CM
authors.lastname: Ho
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung, Taiwan.|Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Fang-Wei
authors.initials: FW
authors.lastname: Hu
authors.affiliation: School of Public Health, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Shiuan-Shinn
authors.initials: SS
authors.lastname: Lee
authors.affiliation: Department of Dental Hygiene, College of Health Care, China Medical University, Taichung, Taiwan.
authors.forename: Tzong-Ming
authors.initials: TM
authors.lastname: Shieh
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: Chuan-Hang
authors.initials: CH
authors.lastname: Yu
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung, Taiwan.|Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Shih-Shen
authors.initials: SS
authors.lastname: Lin
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
mesh_terms: D001114:Areca / Q000009:adverse effects; D001115:Arecoline / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D054443:Cell Migration Assays; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009062:Mouth Neoplasms / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077195:Squamous Cell Carcinoma of Head and Neck; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D001115:Arecoline
keywords: ZEB1; arecoline; oral squamous cell carcinoma