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

Overview of attention for article published in BMC Cancer, May 2017
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Title
Role of peptidylarginine deiminase 2 (PAD2) in mammary carcinoma cell migration
Published in
BMC Cancer, May 2017
DOI 10.1186/s12885-017-3354-x
Pubmed ID
Authors

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

Abstract

Penetration 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. For 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. Our 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. Together, 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.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 47 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 47 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 12 26%
Student > Bachelor 9 19%
Student > Doctoral Student 4 9%
Student > Master 4 9%
Researcher 4 9%
Other 4 9%
Unknown 10 21%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 17 36%
Agricultural and Biological Sciences 5 11%
Medicine and Dentistry 3 6%
Chemistry 3 6%
Pharmacology, Toxicology and Pharmaceutical Science 1 2%
Other 4 9%
Unknown 14 30%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 05 June 2017.
All research outputs
#17,897,310
of 22,977,819 outputs
Outputs from BMC Cancer
#5,003
of 8,348 outputs
Outputs of similar age
#224,027
of 313,455 outputs
Outputs of similar age from BMC Cancer
#74
of 139 outputs
Altmetric has tracked 22,977,819 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 8,348 research outputs from this source. They receive a mean Attention Score of 4.3. This one is in the 34th percentile – i.e., 34% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 313,455 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 23rd percentile – i.e., 23% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 139 others from the same source and published within six weeks on either side of this one. This one is in the 36th percentile – i.e., 36% of its contemporaries scored the same or lower than it.