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

Molecular Biology of the Cell
Cristina ViganóErich A Nigg

Abstract

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 mito...Continue Reading

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Citations

Jan 4, 2019·Nature Cell Biology·Narendra Kumar Chunduri, Zuzana Storchová
Sep 22, 2019·International Journal of Molecular Sciences·David L Newman, Stephen L Gregory
Nov 14, 2018·Cancer Research·Eva Gronroos, Carlos López-García
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Apr 7, 2021·Seminars in Cell & Developmental Biology·Zuzana Storchova
Apr 21, 2021·Expert Review of Proteomics·Olson Tsang, Jason W H Wong
May 7, 2021·Proceedings of the National Academy of Sciences of the United States of America·William N WilliamScott M Lippman
Aug 6, 2021·Developmental Cell·Devon A LukowJason M Sheltzer
Sep 24, 2021·Nature Communications·Narendra Kumar ChunduriZuzana Storchova
Dec 29, 2021·Cellular Oncology (Dordrecht)·Sara Vanessa BernhardZuzana Storchova

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Methods Mentioned

BETA
fluorescence-­activated sorting
flow cytometry
chromosomal aberrations
sumoylation
FACS
Feature Extraction

Software Mentioned

Protein Prophet
MASCOT
GraphPad Prism
SoftWorx
SafeQuant R script
SequenceReverser
msconvert
MetaMorph
Feature Extraction
R package topGO

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