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Survivin and XIAP – two potential biological targets in follicular thyroid carcinoma
Follicular thyroid carcinoma’s (FTC) overall good prognosis deteriorates if the tumour fails to retain radioactive iodine. Therefore, new druggable targets are in high demand for this subset of patients. Here, we investigated the prognostic and biological role of survivin and XIAP in FTC. Survivin a...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5595817/ https://www.ncbi.nlm.nih.gov/pubmed/28900184 http://dx.doi.org/10.1038/s41598-017-11426-3 |
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author | Werner, Thomas A. Dizdar, Levent Nolten, Inga Riemer, Jasmin C. Mersch, Sabrina Schütte, Sina C. Driemel, Christiane Verde, Pablo E. Raba, Katharina Topp, Stefan A. Schott, Matthias Knoefel, Wolfram T. Krieg, Andreas |
author_facet | Werner, Thomas A. Dizdar, Levent Nolten, Inga Riemer, Jasmin C. Mersch, Sabrina Schütte, Sina C. Driemel, Christiane Verde, Pablo E. Raba, Katharina Topp, Stefan A. Schott, Matthias Knoefel, Wolfram T. Krieg, Andreas |
author_sort | Werner, Thomas A. |
collection | PubMed |
description | Follicular thyroid carcinoma’s (FTC) overall good prognosis deteriorates if the tumour fails to retain radioactive iodine. Therefore, new druggable targets are in high demand for this subset of patients. Here, we investigated the prognostic and biological role of survivin and XIAP in FTC. Survivin and XIAP expression was investigated in 44 FTC and corresponding non-neoplastic thyroid specimens using tissue microarrays. Inhibition of both inhibitor of apoptosis proteins (IAP) was induced by shRNAs or specific small molecule antagonists and functional changes were investigated in vitro and in vivo. Survivin and XIAP were solely expressed in FTC tissue. Survivin expression correlated with an advanced tumour stage and recurrent disease. In addition, survivin proved to be an independent negative prognostic marker. Survivin or XIAP knockdown caused a significant reduction in cell viability and proliferation, activated caspase3/7 and was associated with a reduced tumour growth in vivo. IAP-targeting compounds induced a decrease of cell viability, proliferation and cell cycle activity accompanied by an increase in apoptosis. Additionally, YM155 a small molecule inhibitor of survivin expression significantly inhibited tumour growth in vivo. Both IAPs demonstrate significant functional implications in the oncogenesis of FTCs and thus prove to be viable targets in patients with advanced FTC. |
format | Online Article Text |
id | pubmed-5595817 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-55958172017-09-14 Survivin and XIAP – two potential biological targets in follicular thyroid carcinoma Werner, Thomas A. Dizdar, Levent Nolten, Inga Riemer, Jasmin C. Mersch, Sabrina Schütte, Sina C. Driemel, Christiane Verde, Pablo E. Raba, Katharina Topp, Stefan A. Schott, Matthias Knoefel, Wolfram T. Krieg, Andreas Sci Rep Article Follicular thyroid carcinoma’s (FTC) overall good prognosis deteriorates if the tumour fails to retain radioactive iodine. Therefore, new druggable targets are in high demand for this subset of patients. Here, we investigated the prognostic and biological role of survivin and XIAP in FTC. Survivin and XIAP expression was investigated in 44 FTC and corresponding non-neoplastic thyroid specimens using tissue microarrays. Inhibition of both inhibitor of apoptosis proteins (IAP) was induced by shRNAs or specific small molecule antagonists and functional changes were investigated in vitro and in vivo. Survivin and XIAP were solely expressed in FTC tissue. Survivin expression correlated with an advanced tumour stage and recurrent disease. In addition, survivin proved to be an independent negative prognostic marker. Survivin or XIAP knockdown caused a significant reduction in cell viability and proliferation, activated caspase3/7 and was associated with a reduced tumour growth in vivo. IAP-targeting compounds induced a decrease of cell viability, proliferation and cell cycle activity accompanied by an increase in apoptosis. Additionally, YM155 a small molecule inhibitor of survivin expression significantly inhibited tumour growth in vivo. Both IAPs demonstrate significant functional implications in the oncogenesis of FTCs and thus prove to be viable targets in patients with advanced FTC. Nature Publishing Group UK 2017-09-12 /pmc/articles/PMC5595817/ /pubmed/28900184 http://dx.doi.org/10.1038/s41598-017-11426-3 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Werner, Thomas A. Dizdar, Levent Nolten, Inga Riemer, Jasmin C. Mersch, Sabrina Schütte, Sina C. Driemel, Christiane Verde, Pablo E. Raba, Katharina Topp, Stefan A. Schott, Matthias Knoefel, Wolfram T. Krieg, Andreas Survivin and XIAP – two potential biological targets in follicular thyroid carcinoma |
title | Survivin and XIAP – two potential biological targets in follicular thyroid carcinoma |
title_full | Survivin and XIAP – two potential biological targets in follicular thyroid carcinoma |
title_fullStr | Survivin and XIAP – two potential biological targets in follicular thyroid carcinoma |
title_full_unstemmed | Survivin and XIAP – two potential biological targets in follicular thyroid carcinoma |
title_short | Survivin and XIAP – two potential biological targets in follicular thyroid carcinoma |
title_sort | survivin and xiap – two potential biological targets in follicular thyroid carcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5595817/ https://www.ncbi.nlm.nih.gov/pubmed/28900184 http://dx.doi.org/10.1038/s41598-017-11426-3 |
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