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Quantitative proteomic and phosphoproteomic comparison of human colon cancer DLD-1 cells differing in ploidy and chromosome stability

Although aneuploidy is poorly tolerated during embryogenesis, aneuploidy and whole chromosomal instability (CIN) are common hallmarks of cancer, raising the question of how cancer cells can thrive in spite of chromosome aberrations. Here we present a comprehensive and quantitative proteomics analysi...

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Autores principales: Viganó, Cristina, von Schubert, Conrad, Ahrné, Erik, Schmidt, Alexander, Lorber, Thomas, Bubendorf, Lukas, De Vetter, Judith R. F., Zaman, Guido J. R., Storchova, Zuzana, Nigg, Erich A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5921571/
https://www.ncbi.nlm.nih.gov/pubmed/29496963
http://dx.doi.org/10.1091/mbc.E17-10-0577
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author Viganó, Cristina
von Schubert, Conrad
Ahrné, Erik
Schmidt, Alexander
Lorber, Thomas
Bubendorf, Lukas
De Vetter, Judith R. F.
Zaman, Guido J. R.
Storchova, Zuzana
Nigg, Erich A.
author_facet Viganó, Cristina
von Schubert, Conrad
Ahrné, Erik
Schmidt, Alexander
Lorber, Thomas
Bubendorf, Lukas
De Vetter, Judith R. F.
Zaman, Guido J. R.
Storchova, Zuzana
Nigg, Erich A.
author_sort Viganó, Cristina
collection PubMed
description Although aneuploidy is poorly tolerated during embryogenesis, aneuploidy and whole chromosomal instability (CIN) are common hallmarks of cancer, raising the question of how cancer cells can thrive in spite of chromosome aberrations. Here we present a comprehensive and quantitative proteomics analysis of isogenic DLD-1 colorectal adenocarcinoma cells lines, aimed at identifying cellular responses to changes in ploidy and/or CIN. Specifically, we compared diploid (2N) and tetraploid (4N) cells with posttetraploid aneuploid (PTA) clones and engineered trisomic clones. Our study provides a comparative data set on the proteomes and phosphoproteomes of the above cell lines, comprising several thousand proteins and phosphopeptides. In comparison to the parental 2N line, we observed changes in proteins associated with stress responses and with interferon signaling. Although we did not detect a conspicuous protein signature associated with CIN, we observed many changes in phosphopeptides that relate to fundamental cellular processes, including mitotic progression and spindle function. Most importantly, we found that most changes detectable in PTA cells were already present in the 4N progenitor line. This suggests that activation of mitotic pathways through hyper-phosphorylation likely constitutes an important response to chromosomal burden. In line with this conclusion, cells with extensive chromosome gains showed differential sensitivity toward a number of inhibitors targeting cell cycle kinases, suggesting that the efficacy of anti-mitotic drugs may depend on the karyotype of cancer cells.
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spelling pubmed-59215712018-07-16 Quantitative proteomic and phosphoproteomic comparison of human colon cancer DLD-1 cells differing in ploidy and chromosome stability Viganó, Cristina von Schubert, Conrad Ahrné, Erik Schmidt, Alexander Lorber, Thomas Bubendorf, Lukas De Vetter, Judith R. F. Zaman, Guido J. R. Storchova, Zuzana Nigg, Erich A. Mol Biol Cell Articles Although aneuploidy is poorly tolerated during embryogenesis, aneuploidy and whole chromosomal instability (CIN) are common hallmarks of cancer, raising the question of how cancer cells can thrive in spite of chromosome aberrations. Here we present a comprehensive and quantitative proteomics analysis of isogenic DLD-1 colorectal adenocarcinoma cells lines, aimed at identifying cellular responses to changes in ploidy and/or CIN. Specifically, we compared diploid (2N) and tetraploid (4N) cells with posttetraploid aneuploid (PTA) clones and engineered trisomic clones. Our study provides a comparative data set on the proteomes and phosphoproteomes of the above cell lines, comprising several thousand proteins and phosphopeptides. In comparison to the parental 2N line, we observed changes in proteins associated with stress responses and with interferon signaling. Although we did not detect a conspicuous protein signature associated with CIN, we observed many changes in phosphopeptides that relate to fundamental cellular processes, including mitotic progression and spindle function. Most importantly, we found that most changes detectable in PTA cells were already present in the 4N progenitor line. This suggests that activation of mitotic pathways through hyper-phosphorylation likely constitutes an important response to chromosomal burden. In line with this conclusion, cells with extensive chromosome gains showed differential sensitivity toward a number of inhibitors targeting cell cycle kinases, suggesting that the efficacy of anti-mitotic drugs may depend on the karyotype of cancer cells. The American Society for Cell Biology 2018-05-01 /pmc/articles/PMC5921571/ /pubmed/29496963 http://dx.doi.org/10.1091/mbc.E17-10-0577 Text en © 2018 Viganó et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0/ This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License.
spellingShingle Articles
Viganó, Cristina
von Schubert, Conrad
Ahrné, Erik
Schmidt, Alexander
Lorber, Thomas
Bubendorf, Lukas
De Vetter, Judith R. F.
Zaman, Guido J. R.
Storchova, Zuzana
Nigg, Erich A.
Quantitative proteomic and phosphoproteomic comparison of human colon cancer DLD-1 cells differing in ploidy and chromosome stability
title Quantitative proteomic and phosphoproteomic comparison of human colon cancer DLD-1 cells differing in ploidy and chromosome stability
title_full Quantitative proteomic and phosphoproteomic comparison of human colon cancer DLD-1 cells differing in ploidy and chromosome stability
title_fullStr Quantitative proteomic and phosphoproteomic comparison of human colon cancer DLD-1 cells differing in ploidy and chromosome stability
title_full_unstemmed Quantitative proteomic and phosphoproteomic comparison of human colon cancer DLD-1 cells differing in ploidy and chromosome stability
title_short Quantitative proteomic and phosphoproteomic comparison of human colon cancer DLD-1 cells differing in ploidy and chromosome stability
title_sort quantitative proteomic and phosphoproteomic comparison of human colon cancer dld-1 cells differing in ploidy and chromosome stability
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5921571/
https://www.ncbi.nlm.nih.gov/pubmed/29496963
http://dx.doi.org/10.1091/mbc.E17-10-0577
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