Loss of the oligosaccharyl transferase subunit TUSC3 promotes proliferation and migration of ovarian cancer cells

Vaňhara,Petr; Horak,Peter; Pils,Dietmar; Anees,Mariam; Petz,Michaela; Gregor,Wolfgang; Zeillinger,Robert; Krainer,Michael

doi:10.3892/ijo.2013.1824

Loss of the oligosaccharyl transferase subunit TUSC3 promotes proliferation and migration of ovarian cancer cells

Authors:
- Petr Vaňhara
- Peter Horak
- Dietmar Pils
- Mariam Anees
- Michaela Petz
- Wolfgang Gregor
- Robert Zeillinger
- Michael Krainer
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Affiliations: Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic, Department of Internal Medicine I and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria, Department of Obstetrics and Gynecology, Division of Gynecology, Medical University of Vienna, Vienna, Austria, Research Group of Molecular Pharmacology and Toxicology, University of Veterinary Medicine Vienna, Vienna, Austria
Published online on: February 12, 2013 https://doi.org/10.3892/ijo.2013.1824
Pages: 1383-1389

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Abstract

Consequences of deregulated protein N-glycosylation on cancer pathogenesis are poorly understood. TUSC3 is a gene with a putative function in N-glycosylation, located on the short arm of chromosome 8. This is a chromosomal region of frequent genetic loss in ovarian cancer. We established recently that the expression of TUSC3 is epigenetically decreased in epithelial ovarian cancer compared to benign controls and provides prognostic information on patient survival. Therefore, we analyzed the consequences of silenced TUSC3 expression on proliferation, invasion and migration of ovarian cell lines. In addition, we performed subcellular fractionation, co-immunofluorescence and co-immunoprecipitation experiments to establish the molecular localization of TUSC3 in ovarian cancer cells. We demonstrated that TUSC3 is localized in the endoplasmic reticulum as a subunit of the oligosaccharyltransferase complex and is capable of modulation of glycosylation patterning of ovarian cancer cells. Most importantly, silencing of TUSC3 enhances proliferation and migration of ovarian cancer cells in vitro. Our observations suggest a role for N-glycosylating events in ovarian cancer pathogenesis in general, and identify TUSC3 as a tumor suppressor gene in ovarian cancer in particular.

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