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SUMOylation Is Associated with Aggressive Behavior in Chondrosarcoma of Bone

SIMPLE SUMMARY: SUMO is a ubiquitin-like post-translational modification important for many cellular processes and is suggested to play a role in cancer cell cycle progression. The aim of our study is to understand the role of SUMOylation in tumor progression and aggressiveness. Chondrosarcoma of bo...

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Autores principales: Kroonen, Jessie S., Kruisselbrink, Alwine B., Briaire-de Bruijn, Inge H., Olaofe, Olaejirinde O., Bovée, Judith V. M. G., Vertegaal, Alfred C. O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345166/
https://www.ncbi.nlm.nih.gov/pubmed/34359724
http://dx.doi.org/10.3390/cancers13153823
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author Kroonen, Jessie S.
Kruisselbrink, Alwine B.
Briaire-de Bruijn, Inge H.
Olaofe, Olaejirinde O.
Bovée, Judith V. M. G.
Vertegaal, Alfred C. O.
author_facet Kroonen, Jessie S.
Kruisselbrink, Alwine B.
Briaire-de Bruijn, Inge H.
Olaofe, Olaejirinde O.
Bovée, Judith V. M. G.
Vertegaal, Alfred C. O.
author_sort Kroonen, Jessie S.
collection PubMed
description SIMPLE SUMMARY: SUMO is a ubiquitin-like post-translational modification important for many cellular processes and is suggested to play a role in cancer cell cycle progression. The aim of our study is to understand the role of SUMOylation in tumor progression and aggressiveness. Chondrosarcoma of bone was employed as a model to investigate if SUMOylation contributes to its aggressiveness. We confirmed that SUMO expression levels correlate with aggressiveness of chondrosarcoma and disease outcome. Inhibition of SUMOylation showed promising effects on reduction of chondrosarcoma growth in vitro. Our study implies that SUMO expression could be used as a potential biomarker for disease outcome in chondrosarcoma. ABSTRACT: Multiple components of the SUMOylation machinery are deregulated in various cancers and could represent potential therapeutic targets. Understanding the role of SUMOylation in tumor progression and aggressiveness would increase our insight in the role of SUMO in cancer and clarify its potential as a therapeutic target. Here we investigate SUMO in relation to conventional chondrosarcomas, which are malignant cartilage forming tumors of the bone. Aggressiveness of chondrosarcoma increases with increasing histological grade, and a multistep progression model is assumed. High-grade chondrosarcomas have acquired an increased number of genetic alterations. Using immunohistochemistry on tissue microarrays (TMA) containing 137 chondrosarcomas, we showed that higher expression of SUMO1 and SUMO2/3 correlates with increased histological grade. In addition, high SUMO2/3 expression was associated with decreased overall survival chances (p = 0. 0312) in chondrosarcoma patients as determined by log-rank analysis and Cox regression. Various chondrosarcoma cell lines (n = 7), especially those derived from dedifferentiated chondrosarcoma, were sensitive to SUMO inhibition in vitro. Mechanistically, we found that SUMO E1 inhibition interferes with cell division and as a consequence DNA bridges are frequently formed between daughter cells. In conclusion, SUMO expression could potentially serve as a prognostic biomarker.
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spelling pubmed-83451662021-08-07 SUMOylation Is Associated with Aggressive Behavior in Chondrosarcoma of Bone Kroonen, Jessie S. Kruisselbrink, Alwine B. Briaire-de Bruijn, Inge H. Olaofe, Olaejirinde O. Bovée, Judith V. M. G. Vertegaal, Alfred C. O. Cancers (Basel) Article SIMPLE SUMMARY: SUMO is a ubiquitin-like post-translational modification important for many cellular processes and is suggested to play a role in cancer cell cycle progression. The aim of our study is to understand the role of SUMOylation in tumor progression and aggressiveness. Chondrosarcoma of bone was employed as a model to investigate if SUMOylation contributes to its aggressiveness. We confirmed that SUMO expression levels correlate with aggressiveness of chondrosarcoma and disease outcome. Inhibition of SUMOylation showed promising effects on reduction of chondrosarcoma growth in vitro. Our study implies that SUMO expression could be used as a potential biomarker for disease outcome in chondrosarcoma. ABSTRACT: Multiple components of the SUMOylation machinery are deregulated in various cancers and could represent potential therapeutic targets. Understanding the role of SUMOylation in tumor progression and aggressiveness would increase our insight in the role of SUMO in cancer and clarify its potential as a therapeutic target. Here we investigate SUMO in relation to conventional chondrosarcomas, which are malignant cartilage forming tumors of the bone. Aggressiveness of chondrosarcoma increases with increasing histological grade, and a multistep progression model is assumed. High-grade chondrosarcomas have acquired an increased number of genetic alterations. Using immunohistochemistry on tissue microarrays (TMA) containing 137 chondrosarcomas, we showed that higher expression of SUMO1 and SUMO2/3 correlates with increased histological grade. In addition, high SUMO2/3 expression was associated with decreased overall survival chances (p = 0. 0312) in chondrosarcoma patients as determined by log-rank analysis and Cox regression. Various chondrosarcoma cell lines (n = 7), especially those derived from dedifferentiated chondrosarcoma, were sensitive to SUMO inhibition in vitro. Mechanistically, we found that SUMO E1 inhibition interferes with cell division and as a consequence DNA bridges are frequently formed between daughter cells. In conclusion, SUMO expression could potentially serve as a prognostic biomarker. MDPI 2021-07-29 /pmc/articles/PMC8345166/ /pubmed/34359724 http://dx.doi.org/10.3390/cancers13153823 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kroonen, Jessie S.
Kruisselbrink, Alwine B.
Briaire-de Bruijn, Inge H.
Olaofe, Olaejirinde O.
Bovée, Judith V. M. G.
Vertegaal, Alfred C. O.
SUMOylation Is Associated with Aggressive Behavior in Chondrosarcoma of Bone
title SUMOylation Is Associated with Aggressive Behavior in Chondrosarcoma of Bone
title_full SUMOylation Is Associated with Aggressive Behavior in Chondrosarcoma of Bone
title_fullStr SUMOylation Is Associated with Aggressive Behavior in Chondrosarcoma of Bone
title_full_unstemmed SUMOylation Is Associated with Aggressive Behavior in Chondrosarcoma of Bone
title_short SUMOylation Is Associated with Aggressive Behavior in Chondrosarcoma of Bone
title_sort sumoylation is associated with aggressive behavior in chondrosarcoma of bone
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345166/
https://www.ncbi.nlm.nih.gov/pubmed/34359724
http://dx.doi.org/10.3390/cancers13153823
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