title: Inhibition of KL-6/MUC1 glycosylation limits aggressive progression of pancreatic cancer.
abstract: OBJECTIVE
  To evaluate the significance of KL-6/MUC1 (a type of MUC1) glycosylation in pancreatic cancer progression.
  
  
  METHODS
  KL-6/MUC1 expression was detected by immunohistochemistry in 48 patients with pancreatic duct cell carcinoma. The N-/O-glycosylation inhibitors (tunicamycin and benzyl-N-acetyl-α-galactosaminide) were then used to interfere with KL-6/MUC1 glycosylation in two pancreatic carcinoma cell lines, and the effects on KL-6/MUC1 expression, and cell adhesion and invasion were determined. In addition, protein expression of epithelial-mesenchymal transition markers, E-cadherin and vimentin, were evaluated in cells after treatment with glycosylation inhibitors.
  
  
  RESULTS
  Overexpression of KL-6/MUC1 was found in all pancreatic cancer tissues, but not in the surrounding normal pancreatic tissues. The expression profile of KL-6/MUC1 was significantly decreased after treatment with the inhibitors. The adhesion and invasive ability of cancer cells were significantly decreased after drug treatment, and increased E-cadherin and decreased vimentin expression were found.
  
  
  CONCLUSIONS
  KL-6/MUC1 glycosylation is involved in pancreatic cancer metastasis and invasion. Therapeutic strategies which target this may help control the aggressive behavior of pancreatic cancer cells.
authors.affiliation: Huan-Li Xu, Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
authors.forename: Huan-Li
authors.initials: HL
authors.lastname: Xu
authors.affiliation: Huan-Li Xu, Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Huan-Li Xu, Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
authors.forename: Ke-Ming
authors.initials: KM
authors.lastname: Zhang
authors.affiliation: Huan-Li Xu, Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.affiliation: Huan-Li Xu, Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kokudo
mesh_terms: D000116:Acetylgalactosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D000231:Adenocarcinoma, Papillary / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD; D000970:Antineoplastic Agents / Q000494:pharmacology; D001593:Benzyl Compounds / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006031:Glycosylation; D006801:Humans; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000378:metabolism* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D014415:Tunicamycin / Q000494:pharmacology; D014746:Vimentin / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000970:Antineoplastic Agents; D001593:Benzyl Compounds; D014408:Biomarkers, Tumor; C513384:CDH1 protein, human; D015820:Cadherins; D004791:Enzyme Inhibitors; C060192:MUC1 protein, human; D018396:Mucin-1; D014746:Vimentin; D014415:Tunicamycin; C080739:benzyl-alpha-N-acetylgalactosamine; D000116:Acetylgalactosamine
keywords: Benzyl-N-acetyl-α-galactosaminide; Glycosylation; KL-6/MUC1; Pancreatic carcinoma; Tunicamycin