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

• Published in: Oncotarget 2019-04, Vol.10 (30), p.2899-2910
• Main Authors: Jaskiewicz, Nicole Morin, Townson, David H
• Format: Article
• Language: English
• Subjects: Research Paper
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.26884

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 ( and ), 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 , 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 ( ). 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.