Evidence map›Paper›PMID 28549415›Full record

ArticleBMC cancer2017

Role of peptidylarginine deiminase 2 (PAD2) in mammary carcinoma cell migration.

Sachi Horibata, Katherine E Rogers, David Sadegh, Lynne J Anguish, John L McElwee, Pragya Shah, Paul R Thompson, Scott A Coonrod

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 12% 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

27 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.

  1. Pooled it
  2. Unveiling nuclear localization signals in human arginine deiminase proteins.Protein science : a publication of the Protein Society · 2026
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  11. Citrullination and the protein code: crosstalk between post-translational modifications in cancer.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023
    Review
  12. Article
  13. Review
  14. The virtues and vices of protein citrullination.Royal Society open science · 2022
    Review
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  16. Article
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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

8 authors at 3 institutions in 1 country.

Sachi HoribataBaker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14850, USA.
Katherine E RogersBaker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14850, USA.
David SadeghBaker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14850, USA.
Lynne J AnguishBaker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14850, USA.
John L McElweeBaker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14850, USA.
Pragya ShahBaker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14850, USA.
Paul R ThompsonDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, 01605, USA.
Scott A CoonrodBaker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14850, USA. sac269@cornell.edu.
Cornell University · USNew York State College of Veterinary Medicine · USUniversity of Massachusetts Chan Medical School · US

Funding

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

Abstract

backgroundPenetration of the mammary gland basement membrane by cancer cells is a crucial first step in tumor invasion. Using a mouse model of ductal carcinoma in situ, we previously found that inhibition of peptidylarginine deiminase 2 (PAD2, aka PADI2) activity appears to maintain basement membrane integrity in xenograft tumors. The goal of this investigation was to gain insight into the mechanisms by which PAD2 mediates this process.

methodsFor our study, we modulated PAD2 activity in mammary ductal carcinoma cells by lentiviral shRNA-mediated depletion, lentiviral-mediated PAD2 overexpression, or PAD inhibition and explored the effects of these treatments on changes in cell migration and cell morphology. We also used these PAD2-modulated cells to test whether PAD2 may be required for EGF-induced cell migration. To determine how PAD2 might promote tumor cell migration in vivo, we tested the effects of PAD2 inhibition on the expression of several cell migration mediators in MCF10DCIS.com xenograft tumors. In addition, we tested the effect of PAD2 inhibition on EGF-induced ductal invasion and elongation in primary mouse mammary organoids. Lastly, using a transgenic mouse model, we investigated the effects of PAD2 overexpression on mammary gland development.

resultsOur results indicate that PAD2 depletion or inhibition suppresses cell migration and alters the morphology of MCF10DCIS.com cells. In addition, we found that PAD2 depletion suppresses the expression of the cytoskeletal regulatory proteins RhoA, Rac1, and Cdc42 and also promotes a mesenchymal to epithelial-like transition in tumor cells with an associated increase in the cell adhesion marker, E-cadherin. Our mammary gland organoid study found that inhibition of PAD2 activity suppresses EGF-induced ductal invasion. In vivo, we found that PAD2 overexpression causes hyperbranching in the developing mammary gland.

conclusionTogether, these results suggest that PAD2 plays a critical role in breast cancer cell migration. Our findings that EGF treatment increases protein citrullination and that PAD2 inhibition blocks EGF-induced cell migration suggest that PAD2 likely functions within the EGF signaling pathway to mediate cell migration.

Indexed as

AnimalsCarcinoma, Intraductal, NoninfiltratingCell Line, TumorCell MovementFemaleHumansMammary Neoplasms, ExperimentalMiceMice, TransgenicOrganoidsProtein-Arginine DeiminasesProtein-Arginine DeiminasesDuctal invasionMammary hyperbranchingPeptidylarginine deiminase 2 (PAD2)Tumor cell migration

Identifiers

PMID28549415
PMCPMC5446677
OpenAlexW2618886090

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.