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

被引:34
|
作者
Vigano, Cristina [1 ]
von Schubert, Conrad [1 ]
Ahrne, Erik [1 ]
Schmidt, Alexander [1 ]
Lorber, Thomas [2 ]
Bubendorf, Lukas [2 ]
De Vetter, Judith R. F. [3 ]
Zaman, Guido J. R. [3 ]
Storchova, Zuzana [4 ]
Nigg, Erich A. [1 ]
机构
[1] Univ Basel, Biozentrum, CH-4056 Basel, Switzerland
[2] Univ Basel, Univ Basel Hosp, Inst Pathol, CH-4056 Basel, Switzerland
[3] Netherlands Translat Res Ctr BV, NL-5340 Oss, Netherlands
[4] Univ Kaiserslautern, D-3049 Kaiserslautern, Germany
基金
瑞士国家科学基金会;
关键词
GENE-EXPRESSION; DNA-DAMAGE; MIS-SEGREGATION; DOWNS-SYNDROME; ANEUPLOIDY; INSTABILITY; GENOME; ERRORS; TUMOR; PROLIFERATION;
D O I
10.1091/mbc.E17-10-0577
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:1031 / 1047
页数:17
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