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.

Clinical Institute of Pathology Medical University of Vienna Austria

Department of Histology and Embryology Faculty of Medicine Masaryk University Brno Czech Republic

Department of Obstetrics and Gynecology Molecular Oncology Group Medical University of Vienna Austria

Division of Oncology Department of Internal Medicine 1 and Comprehensive Cancer Center Medical University of Vienna Austria

Institute for Cancer Research Department of Medicine 1 and Comprehensive Cancer Center Medical University of Vienna Austria

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TUSC3: functional duality of a cancer gene