| Title |
Simvastatin prevents triple-negative breast cancer metastasis in pre-clinical models through regulation of FOXO3a
|
|---|---|
| Published in |
Breast Cancer Research and Treatment, November 2015
|
| DOI | 10.1007/s10549-015-3645-3 |
| Pubmed ID | |
| Authors |
Adam R. Wolfe, Bisrat G. Debeb, Lara Lacerda, Richard Larson, Arvind Bambhroliya, Xuelin Huang, Francois Bertucci, Pascal Finetti, Daniel Birnbaum, Steven Van Laere, Parmeswaran Diagaradjan, Brian Ruffell, Nicholaus J. Trenton, Khoi Chu, Walter Hittelman, Michael Diehl, Ilya Levental, Naoto T. Ueno, Wendy A. Woodward |
| Abstract |
We previously reported using statins was correlated with improved metastasis-free survival in aggressive breast cancer. The purpose of this study was to examine the effect of statins on metastatic colonization by triple-negative breast cancer (TNBC) cells. TNBC cell lines were treated with simvastatin and then studied for cell cycle progression and proliferation in vitro, and metastasis formation in vivo, following injection of statin-treated cells. Reverse-phase protein assay (RPPA) analysis was performed on statin-treated and control breast cancer cells. RNA interference targeting FOXO3a was used to measure the impact of simvastatin on FOXO3a-expressing cells. The prognostic value of FOXO3a mRNA expression was examined in eight public breast cancer gene expression datasets including 1479 patients. Simvastatin increased G1/S-phase arrest of the cell cycle and inhibited both proliferation and migration of TNBC cells in vitro. In vitro pre-treatment and in vivo treatment with simvastatin reduced metastases. Phosphorylated FOXO3a was downregulated after simvastatin treatment in (RPPA) analysis. Ectopic expression of FOXO3a enhanced mammosphere formation and migratory capacity in vitro. Knockdown of FOXO3a attenuated the effect of simvastatin on mammosphere formation and migration. Analysis of public gene expression data demonstrates FOXO3a mRNA downregulation was independently associated with shorter metastasis-free survival in all breast cancers, as well as in TNBC breast cancers. Simvastatin inhibits in vitro endpoints associated with metastasis through a FOXO3a mechanism and reduced metastasis formation in vivo. FOXO3a expression is prognostic for metastasis formation in patient data. Further investigation of simvastatin as a cancer therapy is warranted. |
X Demographics
The data shown below were collected from the profiles of 9 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 5 | 56% |
| Japan | 1 | 11% |
| Unknown | 3 | 33% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 7 | 78% |
| Scientists | 1 | 11% |
| Practitioners (doctors, other healthcare professionals) | 1 | 11% |
Mendeley readers
The data shown below were compiled from readership statistics for 74 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Netherlands | 1 | 1% |
| Unknown | 73 | 99% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 15 | 20% |
| Student > Master | 12 | 16% |
| Student > Bachelor | 11 | 15% |
| Student > Ph. D. Student | 7 | 9% |
| Student > Doctoral Student | 6 | 8% |
| Other | 13 | 18% |
| Unknown | 10 | 14% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 17 | 23% |
| Medicine and Dentistry | 13 | 18% |
| Agricultural and Biological Sciences | 9 | 12% |
| Pharmacology, Toxicology and Pharmaceutical Science | 8 | 11% |
| Immunology and Microbiology | 4 | 5% |
| Other | 9 | 12% |
| Unknown | 14 | 19% |
Attention Score in Context
This research output has an Altmetric Attention Score of 6. 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 24 November 2015.
All research outputs
#5,609,287
of 22,833,393 outputs
Outputs from Breast Cancer Research and Treatment
#1,233
of 4,659 outputs
Outputs of similar age
#85,957
of 386,452 outputs
Outputs of similar age from Breast Cancer Research and Treatment
#19
of 73 outputs
Altmetric has tracked 22,833,393 research outputs across all sources so far. Compared to these this one has done well and is in the 75th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 4,659 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.2. This one has gotten more attention than average, scoring higher than 73% of its peers.
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 386,452 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 77% of its contemporaries.
We're also able to compare this research output to 73 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 73% of its contemporaries.