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.

Original languageEnglish (US)
Pages (from-to)1376-1386
Number of pages11
JournalBritish journal of cancer
Volume114
Issue number12
DOIs
StatePublished - Jun 14 2016

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N-Acetylgalactosaminyltransferases
Pancreatic Neoplasms
Glycosylation
Adenocarcinoma
Endothelium
Glycosyltransferases
Growth
Transferases
Lectins
Polysaccharides
Neoplasms
Western Blotting
Immunohistochemistry
Phosphorylation
Staining and Labeling
Neoplasm Metastasis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

@article{9b18dd4fc4ff495c98acb4633761d0f0,
title = "Loss of N-acetylgalactosaminyltransferase 3 in poorly differentiated pancreatic cancer: Augmented aggressiveness and aberrant ErbB family glycosylation",
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 = "Seema Chugh and Meza, {Jane L} and Sheinin, {Yuri M.} and {Palanimuthu Ponnusamy}, Moorthy and Batra, {Surinder Kumar}",
year = "2016",
month = "6",
day = "14",
doi = "10.1038/bjc.2016.116",
language = "English (US)",
volume = "114",
pages = "1376--1386",
journal = "British Journal of Cancer",
issn = "0007-0920",
publisher = "Nature Publishing Group",
number = "12",

}

TY - JOUR

T1 - Loss of N-acetylgalactosaminyltransferase 3 in poorly differentiated pancreatic cancer

T2 - Augmented aggressiveness and aberrant ErbB family glycosylation

AU - Chugh, Seema

AU - Meza, Jane L

AU - Sheinin, Yuri M.

AU - Palanimuthu Ponnusamy, Moorthy

AU - Batra, Surinder Kumar

PY - 2016/6/14

Y1 - 2016/6/14

N2 - 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.

AB - 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.

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U2 - 10.1038/bjc.2016.116

DO - 10.1038/bjc.2016.116

M3 - Article

VL - 114

SP - 1376

EP - 1386

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 12

ER -