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

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.

• Authors: Petr Vaňhara, Peter Horak, Dietmar Pils, Mariam Anees, Michaela Petz, Wolfgang Gregor, Robert Zeillinger, Michael Krainer
• Journal: International journal of oncology (Int J Oncol) Vol. 42 Issue 4 Pg. 1383-9 (Apr 2013) ISSN: 1791-2423 [Electronic] Greece
• PMID: 23404293 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Membrane Proteins
• Protein Subunits
• RNA, Small Interfering
• TUSC3 protein, human
• Tumor Suppressor Proteins
• Hexosyltransferases
• dolichyl-diphosphooligosaccharide - protein glycotransferase

Topics

• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Endoplasmic Reticulum (enzymology)
• Female
• Gene Knockdown Techniques
• Glycosylation
• Hexosyltransferases (genetics, metabolism)
• Humans
• Membrane Proteins (genetics, metabolism)
• Ovarian Neoplasms
• Protein Processing, Post-Translational
• Protein Subunits (genetics, metabolism)
• RNA, Small Interfering (genetics)
• Tumor Suppressor Proteins (genetics, metabolism)