title: MUC20 promotes aggressive phenotypes of epithelial ovarian cancer cells via activation of the integrin β1 pathway.
abstract: OBJECTIVE
  Mucin (MUC) 20 has recently been implicated to play a role in human carcinogenesis. However, the role of MUC20 in epithelial ovarian cancer (EOC) remains to be elucidated.
  
  
  METHODS
  MUC20 expression was assessed in tissue microarray and tumor specimens of EOC patients by immunohistochemistry. Effects of MUC20 on cell viability, adhesion, migration, and invasion were analyzed in MUC20 overexpressing or knockdown EOC cells. Western blotting was performed to analyze signaling pathways modulated by MUC20.
  
  
  RESULTS
  MUC20 was overexpressed in EOC samples compared with benign tissues. High MUC20 expression was significantly associated with poor overall survival in patients with advanced-stage disease. MUC20 overexpression significantly enhanced EOC cell migration and invasion, but not viability. Mechanistic investigations showed that MUC20 increased cell adhesion to extracellular matrix (ECM) proteins and enhanced activation of integrin β1 and phosphorylation of focal adhesion kinase (FAK). The enhancement of cell motility and the integrin β1 signaling by MUC20 was significantly suppressed by integrin β1 blocking antibody. Furthermore, these effects of MUC20 on EOC cells were also demonstrated in MUC20 knockdown cells.
  
  
  CONCLUSIONS
  Our results suggest that MUC20 enhances aggressive behaviors of EOC cells by activating integrin β1 signaling and provide novel insights into the role of MUC20 in ovarian cancer metastasis.
authors.affiliation: Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Chi-Hau
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Ming-Kwang
authors.initials: MK
authors.lastname: Shyu
authors.affiliation: Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Shu-Wei
authors.initials: SW
authors.lastname: Wang
authors.affiliation: Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Chih-Hsing
authors.initials: CH
authors.lastname: Chou
authors.affiliation: Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Miao-Juei
authors.initials: MJ
authors.lastname: Huang
authors.affiliation: Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Tzu-Chi
authors.initials: TC
authors.lastname: Lin
authors.affiliation: Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Syue-Ting
authors.initials: ST
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Ho-Hsiung
authors.initials: HH
authors.lastname: Lin
authors.affiliation: Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan; Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: mchuang@ntu.edu.tw.
authors.forename: Min-Chuan
authors.initials: MC
authors.lastname: Huang
mesh_terms: D000077216:Carcinoma, Ovarian Epithelial; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D009077:Mucins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype; D015398:Signal Transduction
chemical_list: D019012:Integrin beta1; C490965:MUC20 protein, human; D009077:Mucins
keywords: FAK; Integrin; MUC20; Mucin; Ovarian cancer