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Loss of N-acetylgalactosaminyltransferase 3 in poorly differentiated pancreatic cancer: augmented aggressiveness and aberrant ErbB family glycosylation. Br J Cancer 2016 Jun 14;114(12):1376-86

Date

05/18/2016

Pubmed ID

27187683

Pubmed Central ID

PMC4984453

DOI

10.1038/bjc.2016.116

Scopus ID

2-s2.0-84969194701   33 Citations

Abstract

BACKGROUND: Aberrant glycosylation of several proteins underlie pancreatic ductal adenocarcinoma (PDAC) progression and metastasis. O-glycosylation is initiated by a family of enzymes known as polypeptide N-acetylgalactosaminyl transferases (GalNAc-Ts/GALNTs). In this study, we investigated the role of the O-glycosyltransferase GALNT3 in PDAC.

METHODS: Immunohistochemistry staining of GALNT3 was performed on normal, inflammatory and neoplastic pancreatic tissues. Several in vitro functional assays such as proliferation, colony formation, migration and tumour-endothelium adhesion assay were conducted in GALNT3 knockdown PDAC cells to investigate its role in disease aggressiveness. Expression of signalling molecules involved in growth and motility was evaluated using western blotting. Effect of GALNT3 knockdown on glycosylation was examined by lectin pull-down assay.

RESULTS: N-acetylgalactosaminyl transferase 3 expression is significantly decreased in poorly differentiated PDAC cells and tissues as compared with well/moderately differentiated PDAC. Further, knockdown of GALNT3 resulted in increased expression of poorly differentiated PDAC markers, augmented growth, motility and tumour-endothelium adhesion. Pull-down assay revealed that O-glycans (Tn and T) on EGFR and Her2 were altered in PDAC cells, which was accompanied by their increased phosphorylation.

CONCLUSIONS: Our study indicates that loss of GALNT3 occurs in poorly differentiated PDAC, which is associated with the increased aggressiveness and altered glycosylation of ErbB family proteins.

Author List

Chugh S, Meza J, Sheinin YM, Ponnusamy MP, Batra SK

Author

Yuri M. Sheinin MD, PhD Assistant Professor in the Pathology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Carcinoma, Pancreatic Ductal
Cell Differentiation
Cell Line, Tumor
Cell Movement
Cell Proliferation
Endothelial Cells
ErbB Receptors
Gene Knockdown Techniques
Glycosylation
Humans
Immunohistochemistry
N-Acetylgalactosaminyltransferases
Pancreatic Neoplasms
Phosphorylation