Tumor suppressor candidate 3 (TUSC3) prevents the epithelial-to-mesenchymal transition and inhibits tumor growth by modulating the endoplasmic reticulum stress response in ovarian cancer cells.
Ovarian cancer is one of the most common malignancies in women and contributes greatly to cancer-related deaths. Tumor suppressor candidate 3 (TUSC3) is a putative tumor suppressor gene located at chromosomal region 8p22, which is often lost in epithelial cancers. Epigenetic silencing of TUSC3 has been associated with poor prognosis, and hypermethylation of its promoter provides an independent biomarker of overall and disease-free survival in ovarian cancer patients. TUSC3 is localized to the endoplasmic reticulum in an oligosaccharyl tranferase complex responsible for the N-glycosylation of proteins. However, the precise molecular role of TUSC3 in ovarian cancer remains unclear. In this study, we establish TUSC3 as a novel ovarian cancer tumor suppressor using a xenograft mouse model and demonstrate that loss of TUSC3 alters the molecular response to endoplasmic reticulum stress and induces hallmarks of the epithelial-to-mesenchymal transition in ovarian cancer cells. In summary, we have confirmed the tumor-suppressive function of TUSC3 and identified the possible mechanism driving TUSC3-deficient ovarian cancer cells toward a malignant phenotype.
Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.|Center of Biomolecular and Cellular Engineering, International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic.
Kateřina
K
Kratochvílová
Department of Internal Medicine I and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Peter
P
Horak
Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Milan
M
Ešner
Center of Biomolecular and Cellular Engineering, International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic.|Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Brno, Czech Republic.|Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.
Karel
K
Souček
Department of Obstetrics and Gynecology, Molecular Oncology Group, Medical University of Vienna, Vienna, Austria.
Dietmar
D
Pils
Department of Internal Medicine I and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.|Department of Biochemistry, Quaid-i-Azam University, Islamabad, Pakistan.
Mariam
M
Anees
Department of Internal Medicine I and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Erwin
E
Tomasich
Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
František
F
Dráfi
Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Veronika
V
Jurtíková
Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Aleš
A
Hampl
Department of Internal Medicine I and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Michael
M
Krainer
Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Petr
P
Vaňhara
D000818:Animals; D045744:Cell Line, Tumor; D059865:Endoplasmic Reticulum Stress / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D016147:Genes, Tumor Suppressor / Q000502:physiology; D064593:Heterografts; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010051:Ovarian Neoplasms / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D008565:Membrane Proteins; C524338:TUSC3 protein, human; D025521:Tumor Suppressor Proteins
N33; TUSC3; endoplasmic reticulum stress; epithelial-to-mesenchymal transition; ovarian cancer; tumor suppressor