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The atypical chemokine receptor CCX‐CKR regulates metastasis of mammary carcinoma via an effect on EMT

Overview of attention for article published in Immunology & Cell Biology, July 2014
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Title
The atypical chemokine receptor CCX‐CKR regulates metastasis of mammary carcinoma via an effect on EMT
Published in
Immunology & Cell Biology, July 2014
DOI 10.1038/icb.2014.58
Pubmed ID
Authors

Yuka Harata‐Lee, Michelle E Turvey, Julie A Brazzatti, Carly E Gregor, Michael P Brown, Mark J Smyth, Iain Comerford, Shaun R McColl

Abstract

Over the last decade, the significance of the homeostatic CC chemokine receptor-7 and its ligands CC chemokine ligand-19 (CCL19) and CCL21, in various types of cancer, particularly mammary carcinoma, has been highlighted. The chemokine receptor CCX-CKR is a high-affinity receptor for these chemokine ligands but rather than inducing classical downstream signalling events promoting migration, it instead sequesters and targets its ligands for degradation, and appears to function as a regulator of the bioavailability of these chemokines in vivo. Therefore, in this study, we tested the hypothesis that local regulation of chemokine levels by CCX-CKR expressed on tumours alters tumour growth and metastasis in vivo. Expression of CCX-CKR on 4T1.2 mouse mammary carcinoma cells inhibited orthotopic tumour growth. However, this effect could not be correlated with chemokine scavenging in vivo and was not mediated by host adaptive immunity. Conversely, expression of CCX-CKR on 4T1.2 cells resulted in enhanced spontaneous metastasis and haematogenous metastasis in vivo. In vitro characterisation of the tumourigenicity of CCX-CKR-expressing 4T1.2 cells suggested accelerated epithelial-mesenchymal transition (EMT) revealed by their more invasive and motile character, lower adherence to the extracellular matrix and to each other, and greater resistance to anoikis. Further analysis of CCX-CKR-expressing 4T1.2 cells also revealed that transforming growth factor (TGF)-β1 expression was increased both at mRNA and protein levels leading to enhanced autocrine phosphorylation of Smad 2/3 in these cells. Together, our data show a novel function for the chemokine receptor CCX-CKR as a regulator of TGF-β1 expression and the EMT in breast cancer cells.Immunology and Cell Biology advance online publication, 15 July 2014; doi:10.1038/icb.2014.58.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 17 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Romania 1 6%
Unknown 16 94%

Demographic breakdown

Readers by professional status Count As %
Student > Master 4 24%
Student > Bachelor 3 18%
Researcher 3 18%
Student > Doctoral Student 2 12%
Student > Ph. D. Student 1 6%
Other 3 18%
Unknown 1 6%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 9 53%
Medicine and Dentistry 2 12%
Immunology and Microbiology 2 12%
Agricultural and Biological Sciences 1 6%
Social Sciences 1 6%
Other 1 6%
Unknown 1 6%
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 07 December 2015.
All research outputs
#17,285,668
of 25,373,627 outputs
Outputs from Immunology & Cell Biology
#1,595
of 1,848 outputs
Outputs of similar age
#144,918
of 241,649 outputs
Outputs of similar age from Immunology & Cell Biology
#12
of 24 outputs
Altmetric has tracked 25,373,627 research outputs across all sources so far. This one is in the 21st percentile – i.e., 21% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,848 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.3. This one is in the 8th percentile – i.e., 8% of its peers scored the same or lower than it.
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We're also able to compare this research output to 24 others from the same source and published within six weeks on either side of this one. This one is in the 29th percentile – i.e., 29% of its contemporaries scored the same or lower than it.