| Title |
Overexpression of ETV4 is associated with poor prognosis in prostate cancer: involvement of uPA/uPAR and MMPs
|
|---|---|
| Published in |
Tumor Biology, December 2014
|
| DOI | 10.1007/s13277-014-2993-7 |
| Pubmed ID | |
| Authors |
Mei Qi, Zhiyan Liu, Chengwu Shen, Lin Wang, Jiping Zeng, Chunni Wang, Congcong Li, Weiwei Fu, Yi Sun, Bo Han |
| Abstract |
ETS gene fusions involving ERG, ETV1, ETV4, ETV5, and FLI1 define a distinct class of prostate cancer (PCa), and this might have a bearing on diagnosis, prognosis, and rational therapeutic targeting. In the current study, we focused on the clinicopathological significance of ETV4 in Chinese PCa patients and the mechanisms whereby ETV4 overexpression mediates tumor invasion in the prostate. Overall, ETV4 overexpression was identified in 30.4 % (45/148) of PCa cases by immunohistochemistry. Accordingly, ETV4 was rearranged in only 1.6 % (2/128) of PCa patients. Clinically, ETV4 overexpression was significantly correlated with Gleason score (P = 0.045) and pathological tumor stage (P = 0.041). Multivariate Cox regression analysis indicated that ETV4 is an unfavorable independent prognostic factor (P = 0.040). Functional studies further showed that small interfering RNA (siRNA) knockdown of ETV4 significantly decreases proliferation and invasion of PC-3 cell and partially reverses epithelial-mesenchymal transition in vitro. Notably, ETV4 knockdown significantly downregulated expression of urokinase plasminogen activator (uPA) and its receptor (uPAR) at messenger RNA (mRNA) and protein levels. Chromatin immunoprecipitation assay demonstrated that ETV4 regulates uPA expression through direct binding to its promoter region. Additionally, ETV4 knockdown was also observed to significantly inhibit expression of matrix metalloproteinase (MMP)-2 and MMP-9. In conclusion, for the first time, our study suggested that ETV4 is an independent poor prognostic factor in Chinese PCa patients. Silencing of ETV4 suppresses invasion of PCa cells by inhibiting the expression of uPA/uPAR as well as MMPs. Further studies will be needed to determine whether ETV4 could be regarded as a potential target for the management and prevention of PCa. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| France | 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 24 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Poland | 1 | 4% |
| Unknown | 23 | 96% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 7 | 29% |
| Other | 2 | 8% |
| Student > Bachelor | 2 | 8% |
| Student > Postgraduate | 2 | 8% |
| Professor > Associate Professor | 2 | 8% |
| Other | 6 | 25% |
| Unknown | 3 | 13% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 7 | 29% |
| Medicine and Dentistry | 6 | 25% |
| Agricultural and Biological Sciences | 2 | 8% |
| Nursing and Health Professions | 1 | 4% |
| Immunology and Microbiology | 1 | 4% |
| Other | 1 | 4% |
| Unknown | 6 | 25% |
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 30 December 2014.
All research outputs
#20,247,117
of 22,775,504 outputs
Outputs from Tumor Biology
#1,834
of 2,622 outputs
Outputs of similar age
#295,712
of 353,071 outputs
Outputs of similar age from Tumor Biology
#104
of 167 outputs
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