A correlation between altered O-GlcNAcylation, migration and with changes in E-cadherin levels in ovarian cancer cells

Exp Cell Res. 2013 Jun 10;319(10):1482-90. doi: 10.1016/j.yexcr.2013.03.013. Epub 2013 Mar 22.

Abstract

O-GlcNAcylation is a dynamic and reversible posttranslational modification of nuclear and cytoplasmic proteins. In recent years, the roles of O-GlcNAcylation in several human malignant tumors have been investigated, and O-GlcNAcylation was found to be linked to cellular features relevant to metastasis. In this study, we modeled four diverse ovarian cancer cells and investigated the effects of O-GlcNAcylation on ovarian cancer cell migration. We found that total O-GlcNAcylation level was elevated in HO-8910PM cells compared to OVCAR3 cells. Additionally, through altering the total O-GlcNAcylation level by OGT silencing or OGA inhibition, we found that the migration of OVCAR3 cells was dramatically enhanced by PUGNAc and Thiamet G treatment, and the migration ability of HO-8910PM cells was significantly inhibited by OGT silencing. Furthermore, we also found that the expression of E-cadherin, an O-GlcNAcylated protein in ovarian cancer cells, was reduced by OGA inhibition in OVCAR3 cells and elevated by OGT silencing in HO-8910PM cells. These results indicate that O-GlcNAcylation could enhance ovarian cancer cell migration and decrease the expression of E-cadherin. Our studies also suggest that O-GlcNAcylation might become another potential target for the therapy of ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine / analogs & derivatives
  • Acetylglucosamine / metabolism*
  • Acetylglucosamine / pharmacology
  • Antigens, CD
  • Blotting, Western
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Catenins / genetics
  • Catenins / metabolism
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Delta Catenin
  • Female
  • Gene Silencing
  • Glycosylation
  • Humans
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism
  • N-Acetylglucosaminyltransferases / metabolism*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Oximes / pharmacology
  • Phenylcarbamates / pharmacology
  • Pyrans / pharmacology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Thiazoles / pharmacology
  • Transfection
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • Catenins
  • Multiprotein Complexes
  • Oximes
  • Phenylcarbamates
  • Pyrans
  • RNA, Messenger
  • RNA, Small Interfering
  • Thiazoles
  • beta Catenin
  • thiamet G
  • N-acetylglucosaminono-1,5-lactone O-(phenylcarbamoyl)oxime
  • N-Acetylglucosaminyltransferases
  • O-GlcNAc transferase
  • Acetylglucosamine
  • Delta Catenin