Oncotarget

Research Papers:

Hyper-O-GlcNAcylation promotes epithelial-mesenchymal transition in endometrial cancer cells

Nicole Morin Jaskiewicz and David H. Townson

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Oncotarget. 2019; 10:2899-2910. https://doi.org/10.18632/oncotarget.26884

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Abstract

Nicole Morin Jaskiewicz1 and David H. Townson2

1 Department of Molecular, Cellular and Biomedical Sciences, University of New Hampshire, Durham, NH, USA

2 Department of Animal and Veterinary Sciences, University of Vermont, Burlington, VT, USA

Correspondence to:

Nicole Morin Jaskiewicz,email: njaskiew@uvm.edu

Keywords: O-GlcNAc; epithelial-mesenchymal transition; endometrial cancer; metastasis; diabetes

Received: April 02, 2018     Accepted: April 03, 2019     Published: April 23, 2019

ABSTRACT

Diabetic women have a 2–3 fold increased risk of developing endometrial cancer, however, the molecular aspects of this risk are not fully understood. This study investigated the alteration of cellular O-GlcNAcylation of proteins as the potential mechanistic connection between these two conditions. The endometrial cancer cell line (Ishikawa) was utilized to study the effect of dysregulation of O-GlcNAcylation on epithelial mesenchymal transition (EMT). Hyper-O-GlcNAcylation (via 1 μM Thiamet-G/ThmG or 25 mM Glucose) enhanced the expression of EMT-associated genes (WNT5B and FOXC2), and protein expression of the EMT adhesion molecule, N-Cadherin. Reorganization of stress filaments (actin filaments), consistent with EMT, was also noted in ThmG-treated cells. Interestingly, Hypo-O-GlcNAcylation (via 50 μM OSMI-1) also upregulated WNT5B, inferring that any disruption to O-GlcNAc cycling impacts EMT. However, Hypo-O-GlcNAcylation reduced overall cellular proliferation/migration and the expression of pro-EMT genes (AHNAK, TGFB2, FGFBP1, CALD1, TFPI2). In summary, disruption of O-GlcNAc cycling (i.e., Hyper- or Hypo-O-GlcNAcylation) promoted EMT at both the molecular and cellular levels, but only Hyper-O-GlcNAcylation provoked cellular proliferation/migration, and cytoskeletal reorganization.


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