title: Correlation of deregulated like-acetylglucosaminyl transferase and aberrant α-dystroglycan expression with human tongue cancer metastasis.
abstract: OBJECTIVE
  The present study examined the correlation of α-dystroglycan (α-DG) expression and like-acetylglucosaminyl transferase (LARGE) with metastasis of human tongue cancer.
  
  
  METHODS
  Fifty human tongue cancer tissues and 2 tongue squamous cell carcinoma cell lines (CAL27 and SCC4) were involved. Immunohistochemistry was used to detect the expression of α-DG and LARGE. Methylation-specific polymerase chain reaction was performed to assess the methylation status of the LARGE gene promoter. CAL27 and SCC4 cells were transfected with exogenous LARGE and treated with 5-aza-2'-deoxycytidine (Aza-dC), respectively. Glycol sites of α-DG were detected by western blotting. In addition, the laminin overlay assay, cell adhesion assay, and invasion assay were performed.
  
  
  RESULTS
  Immunohistochemical results showed that decreased expression of VIA4-1 and IIH6 (antibodies that recognize the glycol sites of α-DG) were correlated with the lymph node metastasis of tongue cancer (n = 50; P = .016 and .025, respectively). Decreased LARGE expression and hypermethylation of the LARGE gene promoter were correlated with lymph node metastasis and α-DG glycosylation in human tongue cancer (n = 50; P = .043 and .015 respectively). In addition, LARGE overexpression and Aza-dC treatment actively led to restoration of functional α-DG expression, elevation of laminin binding, and decrease of migratory ability in cancer cells.
  
  
  CONCLUSIONS
  The results suggested that absent α-DG expression and LARGE deregulation were closely associated with nodal metastasis of tongue cancer. Aberrant α-DG expression and glycosylation were attributed at least in part to the abnormal epigenetic modification of LARGE, especially the hypermethylation of its promoter.
authors.affiliation: PhD Student, State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Han-Zhong
authors.initials: HZ
authors.lastname: Zhang
authors.affiliation: PhD Student, State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Xia
authors.affiliation: PhD Student, State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhu
authors.affiliation: PhD Student, State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.affiliation: PhD Student, State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Song
authors.affiliation: Professor, State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China; Department of Oral and Maxillofacial and Head and Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China. Electronic address: shangzhengjun@hotmail.com.
authors.forename: Zheng-Jun
authors.initials: ZJ
authors.lastname: Shang
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000556:secondary*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D000077209:Decitabine; D049030:Dystroglycans / Q000032:analysis* / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006031:Glycosylation; D006801:Humans; D007150:Immunohistochemistry; D007797:Laminin / Q000032:analysis; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017351:N-Acetylglucosaminyltransferases / Q000032:analysis* / Q000235:genetics; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D014062:Tongue Neoplasms / Q000473:pathology*; D014162:Transfection
chemical_list: C483081:DAG1 protein, human; D004791:Enzyme Inhibitors; D007797:Laminin; D049030:Dystroglycans; D000077209:Decitabine; D015254:DNA Modification Methylases; C117674:LARGE1 protein, human; D017351:N-Acetylglucosaminyltransferases; D001374:Azacitidine