| Title |
Filamin A (FLNA) modulates chemosensitivity to docetaxel in triple-negative breast cancer through the MAPK/ERK pathway
|
|---|---|
| Published in |
Tumor Biology, November 2015
|
| DOI | 10.1007/s13277-015-4357-3 |
| Pubmed ID | |
| Authors |
Pengxin Zhao, Weiyuan Ma, Zhigang Hu, Leilei Zang, Zhisheng Tian, Kaili Zhang |
| Abstract |
A previous RNA interference (RNAi) screen identified filamin A (FLNA) as a potential biomarker to predict chemosensitivity in triple-negative breast cancer (TNBC). However, its ability to modulate chemosensitivity and the underlying mechanism has not been investigated. Genetic manipulation of FLNA expression has been performed in an immortalized noncancerous human mammary epithelial cell line and four TNBC cell lines to investigate its effect on chemosensitivity. Western blot analysis was performed to identify the potential signaling pathway involved. Xenograft mouse model was used to examine the in vivo role of FLNA in modulating chemosensitivity. Overexpression of FLNA conferred chemoresistance to docetaxel in noncancerous human mammary epithelial cells. Knockdown of FLNA sensitized four TNBC cell lines, MDA-MB-231, HCC38, Htb126, and HCC1937 to docetaxel which was reversed by reconstituted FLNA expression. Decreased FLNA expression correlated with decreased activation of ERK. Constitutive activation of ERK2 reversed siFLNA-induced chemosensitization. Inhibition of MEK1 recapitulates the effect of FLNA knockdown. MDA-MB-231 xenograft with FLNA knockdown showed enhanced response to docetaxel compared with control xenograft with increased apoptosis. FLNA can function as a modulator of chemosensitivity to docetaxel in TNBC cells through regulation of the MAPK/ERK pathway both in vitro and in vivo. FLNA may serve as a novel therapeutic target for improvement of chemotherapy efficacy in TNBC. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 23 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 23 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 4 | 17% |
| Student > Postgraduate | 3 | 13% |
| Researcher | 3 | 13% |
| Student > Bachelor | 3 | 13% |
| Student > Master | 2 | 9% |
| Other | 2 | 9% |
| Unknown | 6 | 26% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 6 | 26% |
| Biochemistry, Genetics and Molecular Biology | 4 | 17% |
| Medicine and Dentistry | 2 | 9% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 4% |
| Nursing and Health Professions | 1 | 4% |
| Other | 3 | 13% |
| Unknown | 6 | 26% |
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 08 November 2015.
All research outputs
#20,983,210
of 23,613,071 outputs
Outputs from Tumor Biology
#1,851
of 2,614 outputs
Outputs of similar age
#241,206
of 287,180 outputs
Outputs of similar age from Tumor Biology
#184
of 303 outputs
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