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CHEK2 represses breast stromal fibroblasts and their paracrine tumor-promoting effects through suppressing SDF-1 and IL-6

Overview of attention for article published in BMC Cancer, August 2016
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Title
CHEK2 represses breast stromal fibroblasts and their paracrine tumor-promoting effects through suppressing SDF-1 and IL-6
Published in
BMC Cancer, August 2016
DOI 10.1186/s12885-016-2614-5
Pubmed ID
Authors

Maha A. Al-Rakan, Siti-Faujiah Hendrayani, Abdelilah Aboussekhra

Abstract

Active fibroblasts, the predominant and the most active cells of breast cancer stroma, are responsible for tumor growth and spread. However, the molecular mediators and pathways responsible for stromal fibroblast activation, and their paracrine pro-carcinogenic effects are still not well defined. The CHEK2 tumor suppressor gene codes for a protein kinase, which plays important roles in the cellular response to various genotoxic stresses. Immunoblotting, quantitative RT-PCR and Immunofluorescence were used to assess the expression of CHEK2 in different primary breast fibroblasts and in tissues. The effect of CHEK2 on the expression and secretion of SDF-1 and IL-6 was evaluated by immunoblotting and ELISA. The WST-1 colorimetric assay was used to assess cell proliferation, while the BD BioCoat Matrigel invasion chambers were utilized to determine the effects of CHEK2 on the migratory and the invasiveness capacities of breast stromal fibroblasts as well as breast cancer cells. We have shown that CHEK2 is down-regulated in most cancer-associated fibroblasts (CAFs) as compared to their corresponding tumor counterpart fibroblasts (TCFs) at both the mRNA and protein levels. Interestingly, CHEK2 down-regulation using specific siRNA increased the expression/secretion of both cancer-promoting cytokines SDF-1 and IL-6, and transdifferentiated stromal fibroblasts to myofibroblasts. These cells were able to enhance the proliferation of non-cancerous epithelial cells, and also boosted the migration/invasion abilities of breast cancer cells in a paracrine manner. The later effect was SDF-1/IL-6-dependent. Importantly, ectopic expression of CHEK2 in active CAFs converted these cells to a normal state, with lower migration/invasion capacities and reduced paracrine pro-carcinogenic effects. These results indicate that CHEK2 possesses non-cell-autonomous tumor suppressor functions, and present the Chk2 protein as an important mediator in the functional interplay between breast carcinomas and their stromal fibroblasts.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 12 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 12 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 3 25%
Student > Ph. D. Student 2 17%
Student > Bachelor 2 17%
Professor > Associate Professor 1 8%
Unknown 4 33%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 4 33%
Agricultural and Biological Sciences 2 17%
Immunology and Microbiology 1 8%
Medicine and Dentistry 1 8%
Unknown 4 33%
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 18 April 2017.
All research outputs
#18,466,751
of 22,881,964 outputs
Outputs from BMC Cancer
#5,441
of 8,326 outputs
Outputs of similar age
#283,793
of 366,909 outputs
Outputs of similar age from BMC Cancer
#161
of 274 outputs
Altmetric has tracked 22,881,964 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 8,326 research outputs from this source. They receive a mean Attention Score of 4.3. This one is in the 21st percentile – i.e., 21% of its peers scored the same or lower than it.
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We're also able to compare this research output to 274 others from the same source and published within six weeks on either side of this one. This one is in the 28th percentile – i.e., 28% of its contemporaries scored the same or lower than it.