Evidence map›Paper›PMID 24247723›Full record

ArticleCancer research2014

Proteogenomic analysis reveals unanticipated adaptations of colorectal tumor cells to deficiencies in DNA mismatch repair.

Patrick J Halvey, Xiaojing Wang, Jing Wang, Ajaz A Bhat, Punita Dhawan, Ming Li, Bing Zhang, Daniel C Liebler, Robbert J C Slebos

Abstract read
In one paragraph

Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Association of C722T polymorphism in XRCC3 gene with larynx cancer: a meta-analysis.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014
    Pooled it
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  12. Precise characterization of KRAS4b proteoforms in human colorectal cells and tumors reveals mutation/modification cross-talk.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  13. Article
  14. Methods, Tools and Current Perspectives in Proteogenomics.Molecular & cellular proteomics : MCP · 2017
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Patrick J HalveyAuthors' Affiliations: Departments of Biochemistry, Biomedical Informatics, Surgery, Cancer Biology, and Biostatistics; and Jim Ayers Institute for Precancer Detection and Diagnosis, Vanderbilt University School of Medicine, Nashville, Tennessee.
Xiaojing Wang
Jing Wang
Ajaz A Bhat
Punita Dhawan
Ming Li
Bing Zhang
Daniel C Liebler
Robbert J C Slebos

Funding

Understanding and Controlling p120 Dysfunction in CRCP50CA095103 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI COFFEY, ROBERT J. · 2002 to 2017
$33.6M
Vanderbilt Proteome Characterization CenterU24CA159988 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI LIEBLER, DANIEL C · 2011 to 2016
$13.9M
Clinical Proteomic Technology Assessment for CancerU24CA126479 · NCI · VANDERBILT UNIVERSITY · PI LIEBLER, DANIEL C · 2006 to 2010
$7.9M
Systems Approach to the Biological Basis of Colon Cancer MetastasesR01GM088822 · NIGMS · VANDERBILT UNIVERSITY · PI BEAUCHAMP, ROBERT DANIEL, ZHANG, BING · 2009 to 2012
$1.5M
NCI NIH HHS P50 CA095103NCI NIH HHS U24 CA126479NCI NIH HHS U24 CA159988NCI NIH HHS U54CA126479NIGMS NIH HHS R01 GM088822NIGMS NIH HHS R01GM088822PHS HHS U24159988
6 · The paper itself

Abstract

A growing body of genomic data on human cancers poses the critical question of how genomic variations translate to cancer phenotypes. We used standardized shotgun proteomics and targeted protein quantitation platforms to analyze a panel of 10 colon cancer cell lines differing by mutations in DNA mismatch repair (MMR) genes. In addition, we performed transcriptome sequencing (RNA-seq) to enable detection of protein sequence variants from the proteomic data. Biologic replicate cultures yielded highly consistent proteomic inventories with a cumulative total of 6,513 protein groups with a protein false discovery rate of 3.17% across all cell lines. Networks of coexpressed proteins with differential expression based on MMR status revealed impact on protein folding, turnover and transport, on cellular metabolism and on DNA and RNA synthesis and repair. Analysis of variant amino acid sequences suggested higher stability of proteins affected by naturally occurring germline polymorphisms than of proteins affected by somatic protein sequence changes. The data provide evidence for multisystem adaptation to MMR deficiency with a stress response that targets misfolded proteins for degradation through the ubiquitin-dependent proteasome pathway. Enrichment analysis suggested epithelial-to-mesenchymal transition in RKO cells, as evidenced by increased mobility and invasion properties compared with SW480. The observed proteomic profiles demonstrate previously unknown consequences of altered DNA repair and provide an expanded basis for mechanistic interpretation of MMR phenotypes.

Indexed as

DNA Mismatch RepairCell Growth ProcessesCell Line, TumorColorectal NeoplasmsHumansProteomicsSequence Analysis, Protein

Identifiers

PMID24247723
PMCPMC3896054

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.