Evidence map›Paper›PMID 30429478›Full record

ArticleNature communications2018

Colorectal cancer liver metastatic growth depends on PAD4-driven citrullination of the extracellular matrix.

A E Yuzhalin, A N Gordon-Weeks, M L Tognoli, K Jones, B Markelc, R Konietzny, R Fischer, A Muth, E O'Neill, P R Thompson and 4 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers.

0numbers the graph read from it
0cells of the map it votes in
124citing papers in PubMed
12.6field-weighted citation impact, top 1% of its field
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

124 citing papers in PubMed, 185 citations in OpenAlex.

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64 more citing papers are in PubMed but not listed here.

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

14 authors at 3 institutions in 3 countries.

A E YuzhalinCRUK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK. arseniy.yuzhalin@oncology.ox.ac.uk.
A N Gordon-WeeksNuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK.ORCID http://orcid.org/0000-0003-2997-4194
M L TognoliCRUK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK.
K JonesCRUK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK.
B MarkelcCRUK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK.ORCID http://orcid.org/0000-0002-8674-702X
R KonietznyTarget Discovery Institute, Nuffield Department of Medicine, University of Oxford, Roosevelt Drive, Headington, Oxford, OX3 7FZ, UK.
R FischerTarget Discovery Institute, Nuffield Department of Medicine, University of Oxford, Roosevelt Drive, Headington, Oxford, OX3 7FZ, UK.ORCID http://orcid.org/0000-0002-9715-5951
A MuthDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, 01605, USA.
E O'NeillCRUK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK.ORCID http://orcid.org/0000-0002-0060-6278
P R ThompsonDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, 01605, USA.
P J VenablesKennedy Institute of Rheumatology, Nuffield Department of Orthopedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, OX3 7FY, UK.
B M KesslerTarget Discovery Institute, Nuffield Department of Medicine, University of Oxford, Roosevelt Drive, Headington, Oxford, OX3 7FZ, UK.ORCID http://orcid.org/0000-0002-8160-2446
S Y LimCRUK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK.
R J MuschelCRUK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK.
University of Oxford · GBUniversity of Massachusetts Chan Medical School · USJohn Radcliffe Hospital · GB

Funding

Chemical probes to decipher PAD biologyR35GM118112 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Paul R Thompson · 2016 to 2026
$9.5M
Cancer Research UK 16466Cancer Research UK 19277NIGMS NIH HHS R35 GM118112
6 · The paper itself

Abstract

Citrullination of proteins, a post-translational conversion of arginine residues to citrulline, is recognized in rheumatoid arthritis, but largely undocumented in cancer. Here we show that citrullination of the extracellular matrix by cancer cell derived peptidylarginine deiminase 4 (PAD4) is essential for the growth of liver metastases from colorectal cancer (CRC). Using proteomics, we demonstrate that liver metastases exhibit higher levels of citrullination and PAD4 than unaffected liver, primary CRC or adjacent colonic mucosa. Functional significance for citrullination in metastatic growth is evident in murine models where inhibition of citrullination substantially reduces liver metastatic burden. Additionally, citrullination of a key matrix component collagen type I promotes greater adhesion and decreased migration of CRC cells along with increased expression of characteristic epithelial markers, suggesting a role for citrullination in promoting mesenchymal-to-epithelial transition and liver metastasis. Overall, our study reveals the potential for PAD4-dependant citrullination to drive the progression of CRC liver metastasis.

Indexed as

AnimalsCell AdhesionCell MovementCitrullinationCollagen Type IColorectal NeoplasmsEpithelial-Mesenchymal TransitionExtracellular MatrixHCT116 CellsHT29 CellsHumansHydrolasesLiver NeoplasmsMiceNeoplasm MetastasisProtein-Arginine DeiminasesCollagen Type IHydrolasesPADI4 protein, humanpeptidylarginine deiminase 4, mouseProtein-Arginine DeiminasesProtein-Arginine Deiminase Type 4

Identifiers

PMID30429478
PMCPMC6235861
OpenAlexW2899743407

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.