title: TUSC3 loss alters the ER stress response and accelerates prostate cancer growth in vivo.
abstract: Prostate cancer is the most prevalent cancer in males in developed countries. Tumor suppressor candidate 3 (TUSC3) has been identified as a putative tumor suppressor gene in prostate cancer, though its function has not been characterized. TUSC3 shares homologies with the yeast oligosaccharyltransferase (OST) complex subunit Ost3p, suggesting a role in protein glycosylation. We provide evidence that TUSC3 is part of the OST complex and affects N-linked glycosylation in mammalian cells. Loss of TUSC3 expression in DU145 and PC3 prostate cancer cell lines leads to increased proliferation, migration and invasion as well as accelerated xenograft growth in a PTEN negative background. TUSC3 downregulation also affects endoplasmic reticulum (ER) structure and stress response, which results in increased Akt signaling. Together, our findings provide first mechanistic insight in TUSC3 function in prostate carcinogenesis in general and N-glycosylation in particular.
authors.affiliation: Division of Oncology, Department of Internal Medicine I and Comprehensive Cancer Center Medical University of Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Horak
authors.affiliation: Division of Oncology, Department of Internal Medicine I and Comprehensive Cancer Center Medical University of Vienna, Austria.
authors.forename: Erwin
authors.initials: E
authors.lastname: Tomasich
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, Masaryk University Brno, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Vaňhara
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, Masaryk University Brno, Czech Republic.
authors.forename: Kateřina
authors.initials: K
authors.lastname: Kratochvílová
authors.affiliation: Division of Oncology, Department of Internal Medicine I and Comprehensive Cancer Center Medical University of Vienna, Austria.
authors.forename: Mariam
authors.initials: M
authors.lastname: Anees
authors.affiliation: Division of Oncology, Department of Internal Medicine I and Comprehensive Cancer Center Medical University of Vienna, Austria.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Marhold
authors.affiliation: Division of Oncology, Department of Internal Medicine I and Comprehensive Cancer Center Medical University of Vienna, Austria.
authors.forename: Christof E
authors.initials: CE
authors.lastname: Lemberger
authors.affiliation: Division of Oncology, Department of Internal Medicine I and Comprehensive Cancer Center Medical University of Vienna, Austria.
authors.forename: Marion
authors.initials: M
authors.lastname: Gerschpacher
authors.affiliation: Clinical Institute of Pathology, Medical University of Vienna, Austria.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Horvat
authors.affiliation: Institute for Cancer Research, Department of Medicine I and Comprehensive Cancer Center, Medical University of Vienna, Austria.
authors.forename: Maria
authors.initials: M
authors.lastname: Sibilia
authors.affiliation: Department of Obstetrics and Gynecology, Molecular Oncology Group, Medical University of Vienna, Austria.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Pils
authors.affiliation: Division of Oncology, Department of Internal Medicine I and Comprehensive Cancer Center Medical University of Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Krainer
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000648:ultrastructure; D059865:Endoplasmic Reticulum Stress / Q000235:genetics; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006031:Glycosylation; D006602:Hexosyltransferases / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D047368:Tumor Burden; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D008565:Membrane Proteins; C524338:TUSC3 protein, human; D025521:Tumor Suppressor Proteins; D006602:Hexosyltransferases; C551978:STT3B protein, human; C025620:dolichyl-diphosphooligosaccharide - protein glycotransferase; D051057:Proto-Oncogene Proteins c-akt