title: Differential membranous E-cadherin expression, cell proliferation and O-GlcNAcylation between primary and metastatic nodal lesion in colorectal cancer.
abstract: BACKGROUND
  O-GlcNAcylation is an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue. The E-cadherin/β-catenin system, an integral component of epithelial to mesenchymal transition (EMT)/mesenchymal to epithelial transition (MET), is affected through O-GlcNAcylation. The current study examined the status of EMT/MET in both the tumor center and invasive front of the primary colorectal carcinoma (CRC) and metastatic nodal lesions, which were compared to O-GlcNAcylation expression levels in those areas. In addition, the cliniopathological significance of O-GlcNAcylation was studied
  
  
  METHODS
  Immunohistochemical staining for E-cadherin, β-catenin, Snail, O-GlcNAc and Ki67 was performed in 40 primary CRC tissues, 40 nonneoplastic colons, and 17 nodal metastatic lesions. Western blot was also conducted in primary CRC tissue
  
  
  RESULTS
  Membranous E-cadherin expression was lowest in the invasive front, but showed greater increases in metastatic nodal lesions. Moreover, its expression level was negatively correlated with that of nuclear β-catenin and Snail. The Ki67 labeling index (LI) was lowest in the invasive front, and increased in metastatic nodal lesions. Primary CRC showed higher expression of O-GlcNAcylation and O-GlcNAc-transferase (OGT) than nonneoplastic colons. O-GlcNAcylation expression decreased in metastatic nodal lesions compared to the invasive front and tumor center, and was inversely correlated with Ki67 LI. However, O-GlcNAcylation expression was only slightly changed between tumor center and invasive front. In addition, there was no correlation between its expression and the level of nuclear β-catenin, membranous E-cadherin and Snail. No significant relationship was observed between O-GlcNAcylation level and cliniopathological parameters.
  
  
  CONCLUSIONS
  Differential membranous E-cadherin expression, cell proliferation and O-GlcNAcylation in metastatic nodal lesion compared to primary CRC may play role in establishing its lesions; however, these findings are not sufficient to show the role of O-GlcNAcylation in the EMT/MET of CRC.
authors.affiliation: Department of Pathology, Dongguk University College of Medicine, Gyongju, Korea. Electronic address: taejung@mail.dongguk.ac.kr.
authors.forename: Tae Jung
authors.initials: TJ
authors.lastname: Jang
mesh_terms: D000117:Acetylglucosamine / Q000032:analysis*; D015703:Antigens, CD; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D015820:Cadherins / Q000032:analysis*; D002277:Carcinoma / Q000737:chemistry* / Q000556:secondary; D002462:Cell Membrane / Q000737:chemistry*; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006031:Glycosylation; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000737:chemistry* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D011499:Protein Processing, Post-Translational
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C513384:CDH1 protein, human; D015820:Cadherins; D000117:Acetylglucosamine
keywords: Colorectal cancer; Epithelial to mesenchymal transition; Mesenchymal to epithelial transition; O-GlcNAcylation