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The homeoprotein DLX4 controls inducible nitric oxide synthase-mediated angiogenesis in ovarian cancer

Overview of attention for article published in Molecular Cancer, April 2015
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Title
The homeoprotein DLX4 controls inducible nitric oxide synthase-mediated angiogenesis in ovarian cancer
Published in
Molecular Cancer, April 2015
DOI 10.1186/s12943-015-0368-3
Pubmed ID
Authors

Bon Trinh, Song Yi Ko, Dhwani Haria, Nicolas Barengo, Honami Naora

Abstract

Homeobox genes encode transcription factors that control patterning of virtually all organ systems including the vasculature. Tumor angiogenesis is stimulated by several homeobox genes that are overexpressed in tumor cells, but the mechanisms of these genes are poorly understood. In this study, we investigated the mechanisms by which DLX4, a homeobox gene that is associated with increased tumor microvessel density, stimulates ovarian tumor angiogenesis. Expression of DLX4 and nitric oxide synthases was analyzed in publicly available transcriptional profiles of ovarian cancer clinical specimens. Levels of inducible nitric oxide synthase (iNOS) were evaluated by quantitative RT-PCR, flow cytometry and nitric oxide assays using ovarian cancer cell lines in which DLX4 was overexpressed or knocked down. Signal Transducer and Activator of Transcription 1 (STAT1) expression and activity were evaluated by luciferase reporter assays, immunofluorescence staining, Western blot and immunoprecipitation. Endothelial cell growth and tumor angiogenesis were evaluated in in vitro assays and xenograft models. We identified that DLX4 induces expression of iNOS, an enzyme that stimulates angiogenesis by generating nitric oxide. Analysis of datasets of two independent patient cohorts revealed that high DLX4 expression in ovarian cancer is strongly associated with elevated expression of iNOS but not of other nitric oxide synthases. Studies using STAT1-expressing and STAT1-deficient cells revealed that DLX4 interacts with STAT1 and induces iNOS expression in part by stimulating STAT1 activity. Expression of DLX4 in ovarian cancer cells stimulated endothelial cell growth in vitro and increased microvessel density in xenograft models, and these stimulatory effects of DLX4 were abrogated when its induction of iNOS was inhibited. These findings indicate that DLX4 promotes ovarian tumor angiogenesis in part by stimulating iNOS expression.

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The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
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 %
Student > Master 5 42%
Researcher 2 17%
Student > Ph. D. Student 2 17%
Professor 1 8%
Student > Bachelor 1 8%
Other 0 0%
Unknown 1 8%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 5 42%
Medicine and Dentistry 4 33%
Materials Science 1 8%
Agricultural and Biological Sciences 1 8%
Unknown 1 8%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 01 May 2015.
All research outputs
#13,433,099
of 22,800,560 outputs
Outputs from Molecular Cancer
#830
of 1,720 outputs
Outputs of similar age
#127,044
of 263,976 outputs
Outputs of similar age from Molecular Cancer
#18
of 52 outputs
Altmetric has tracked 22,800,560 research outputs across all sources so far. This one is in the 39th percentile – i.e., 39% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,720 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.7. This one is in the 49th percentile – i.e., 49% 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 263,976 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 50% of its contemporaries.
We're also able to compare this research output to 52 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 63% of its contemporaries.