title: GALNT2 enhances migration and invasion of oral squamous cell carcinoma by regulating EGFR glycosylation and activity.
abstract: OBJECTIVE
  Oral squamous cell carcinoma (OSCC) is one of the leading cancers worldwide. Aberrant glycosylation affects many cellular properties in cancers, including OSCC. This study aimed to explore the role of N-acetylgalactosaminyltransferase 2 (GALNT2) in OSCC.
  
  
  METHODS
  Immunohistochemistry was performed to study the expression of GALNT2 in an OSCC tissue microarray. Effects of GALNT2 overexpression and knockdown on cell migration and invasion were analyzed in SAS cells by transwell migration assay and matrigel invasion assay, respectively. The Vicia villosa agglutinin (VVA) pull down assay was conducted to detect changes in O-glycans on acceptor substrates of GALNT2. Cell signaling was analyzed by Western blotting.
  
  
  RESULTS
  GALNT2 was overexpressed in 73% (35/48) of OSCC tissues. Moreover, GALNT2 expression was localized in the invasive front and increased in high grade OSCC. GALNT2 overexpression enhanced migration and invasion of SAS cells triggered by fetal bovine serum (FBS) and epidermal growth factor (EGF). In contrast, GALNT2 knockdown inhibited SAS cell migration and invasion. Furthermore, GALNT2 overexpression enhanced VVA binding to epidermal growth factor receptor (EGFR) and EGF-induced phosphorylation of EGFR and AKT. Conversely, GALNT2 knockdown decreased VVA binding and suppressed activity of EGFR and AKT.
  
  
  CONCLUSIONS
  GALNT2 is frequently overexpressed in OSCC, especially in the carcinoma cells at the invasive front. GALNT2 overexpression enhances the invasive potential of OSCC cells via modifying O-glycosylation and activity of EGFR. These findings suggest that GALNT2 plays an important role in the invasive behavior of OSCC and that targeting GALNT2 could be a promising approach for OSCC therapy.
authors.affiliation: Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Mei-Chun
authors.initials: MC
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.
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: Chiung-Hui
authors.initials: CH
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan; Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: yangtl@ntu.edu.tw.
authors.forename: Tsung-Lin
authors.initials: TL
authors.lastname: Yang
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: D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D017931:DNA Primers; D066246:ErbB Receptors / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*; D017350:N-Acetylgalactosaminyltransferases / Q000502:physiology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D000097763:Polypeptide N-acetylgalactosaminyltransferase
chemical_list: D017931:DNA Primers; D066246:ErbB Receptors; D017350:N-Acetylgalactosaminyltransferases; D034741:RNA, Small Interfering; D000097763:Polypeptide N-acetylgalactosaminyltransferase
keywords: Epidermal growth factor receptor (EGFR); Glycosylation; Glycosyltransferase; Invasion; N-acetylgalactosaminyltransferase 2 (GALNT2); Oral squamous cell carcinoma (OSCC)