↓ Skip to main content

Direct inhibition of ACTN4 by ellagic acid limits breast cancer metastasis via regulation of β-catenin stabilization in cancer stem cells

Overview of attention for article published in Journal of Experimental & Clinical Cancer Research, December 2017
Altmetric Badge

Mentioned by

twitter
1 tweeter

Citations

dimensions_citation
30 Dimensions

Readers on

mendeley
39 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
Direct inhibition of ACTN4 by ellagic acid limits breast cancer metastasis via regulation of β-catenin stabilization in cancer stem cells
Published in
Journal of Experimental & Clinical Cancer Research, December 2017
DOI 10.1186/s13046-017-0635-9
Pubmed ID
Authors

Neng Wang, Qi Wang, Hailin Tang, Fengxue Zhang, Yifeng Zheng, Shengqi Wang, Jin Zhang, Zhiyu Wang, Xiaoming Xie

Abstract

Pharmacology-based target identification has become a novel strategy leading to the discovery of novel pathological biomarkers. Ellagic acid (EA), a dietary polyphenol compound, exhibits potent anticancer activities; however, the underlying mechanisms remain unclear. The current study sought to determine the role and regulation of ACTN4 expression in human breast cancer metastasis and EA-based therapy. The anti-metastasis ability of EA was validated by MMTV-PyMT mice and in vitro cell models. Drug affinity responsive target stability (DARTS) was utilized to identify ACTN4 as the direct target of EA. The metastatic regulated function of ACTN4 were assessed by cancer stem cells (CSCs)-related assays, including mammosphere formation, tumorigenic ability, reattachment differentiation, and signaling pathway analysis. The mechanisms of ACTN4 on β-catenin stabilization were investigated by western blotting, co-immunoprecipitation and ubiquitination assays. The clinical significance of ACTN4 was based on human tissue microarray (TMA) analysis and The Cancer Genome Atlas (TCGA) database exploration. EA inhibited breast cancer growth and metastasis via directly targeting ACTN4 in vitro and in vivo, and was accompanied by a limited CSC population. ACTN4 knockdown resulted in the blockage of malignant cell proliferation, colony formation, and ameliorated metastasis potency. ACTN4-positive CSCs exhibited a higher ESA+ proportion, increased mammosphere-formation ability, and enhanced in vivo tumorigenesis ability. Mechanism exploration revealed that interruption of ACTN4/β-catenin interaction will result in the activation of β-catenin proteasome degradation. Increased ACTN4 expression was directly associated with the advanced cancer stage, an increased incidence of metastasis, and poor overall survival period. Taken together, our results suggest that ACTN4 plays an important role in breast CSCs-related metastasis and is a novel therapeutic target of EA treatment.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 39 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 39 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 9 23%
Student > Master 8 21%
Student > Ph. D. Student 8 21%
Student > Doctoral Student 3 8%
Student > Bachelor 3 8%
Other 3 8%
Unknown 5 13%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 10 26%
Medicine and Dentistry 5 13%
Pharmacology, Toxicology and Pharmaceutical Science 4 10%
Agricultural and Biological Sciences 3 8%
Computer Science 2 5%
Other 6 15%
Unknown 9 23%

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 09 December 2017.
All research outputs
#10,875,504
of 12,271,192 outputs
Outputs from Journal of Experimental & Clinical Cancer Research
#510
of 719 outputs
Outputs of similar age
#285,214
of 344,126 outputs
Outputs of similar age from Journal of Experimental & Clinical Cancer Research
#56
of 78 outputs
Altmetric has tracked 12,271,192 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 719 research outputs from this source. They receive a mean Attention Score of 2.4. This one is in the 1st percentile – i.e., 1% 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 344,126 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 78 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.