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TUSC3 Loss Alters the ER Stress Response and Accelerates Prostate Cancer Growth in vivo

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 oligosaccharyltransfer...

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Autores principales: Horak, Peter, Tomasich, Erwin, Vaňhara, Petr, Kratochvílová, Kateřina, Anees, Mariam, Marhold, Maximilian, Lemberger, Christof E., Gerschpacher, Marion, Horvat, Reinhard, Sibilia, Maria, Pils, Dietmar, Krainer, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894551/
https://www.ncbi.nlm.nih.gov/pubmed/24435307
http://dx.doi.org/10.1038/srep03739
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author Horak, Peter
Tomasich, Erwin
Vaňhara, Petr
Kratochvílová, Kateřina
Anees, Mariam
Marhold, Maximilian
Lemberger, Christof E.
Gerschpacher, Marion
Horvat, Reinhard
Sibilia, Maria
Pils, Dietmar
Krainer, Michael
author_facet Horak, Peter
Tomasich, Erwin
Vaňhara, Petr
Kratochvílová, Kateřina
Anees, Mariam
Marhold, Maximilian
Lemberger, Christof E.
Gerschpacher, Marion
Horvat, Reinhard
Sibilia, Maria
Pils, Dietmar
Krainer, Michael
author_sort Horak, Peter
collection PubMed
description 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.
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spelling pubmed-38945512014-01-17 TUSC3 Loss Alters the ER Stress Response and Accelerates Prostate Cancer Growth in vivo Horak, Peter Tomasich, Erwin Vaňhara, Petr Kratochvílová, Kateřina Anees, Mariam Marhold, Maximilian Lemberger, Christof E. Gerschpacher, Marion Horvat, Reinhard Sibilia, Maria Pils, Dietmar Krainer, Michael Sci Rep Article 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. Nature Publishing Group 2014-01-17 /pmc/articles/PMC3894551/ /pubmed/24435307 http://dx.doi.org/10.1038/srep03739 Text en Copyright © 2014, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Article
Horak, Peter
Tomasich, Erwin
Vaňhara, Petr
Kratochvílová, Kateřina
Anees, Mariam
Marhold, Maximilian
Lemberger, Christof E.
Gerschpacher, Marion
Horvat, Reinhard
Sibilia, Maria
Pils, Dietmar
Krainer, Michael
TUSC3 Loss Alters the ER Stress Response and Accelerates Prostate Cancer Growth in vivo
title TUSC3 Loss Alters the ER Stress Response and Accelerates Prostate Cancer Growth in vivo
title_full TUSC3 Loss Alters the ER Stress Response and Accelerates Prostate Cancer Growth in vivo
title_fullStr TUSC3 Loss Alters the ER Stress Response and Accelerates Prostate Cancer Growth in vivo
title_full_unstemmed TUSC3 Loss Alters the ER Stress Response and Accelerates Prostate Cancer Growth in vivo
title_short TUSC3 Loss Alters the ER Stress Response and Accelerates Prostate Cancer Growth in vivo
title_sort tusc3 loss alters the er stress response and accelerates prostate cancer growth in vivo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894551/
https://www.ncbi.nlm.nih.gov/pubmed/24435307
http://dx.doi.org/10.1038/srep03739
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