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Tumor microenvironment-based feed-forward regulation of NOS2 in breast cancer progression

Overview of attention for article published in Proceedings of the National Academy of Sciences of the United States of America, April 2014
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About this Attention Score

  • Above-average Attention Score compared to outputs of the same age (62nd percentile)

Mentioned by

twitter
3 tweeters

Citations

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93 Dimensions

Readers on

mendeley
80 Mendeley
citeulike
2 CiteULike
Title
Tumor microenvironment-based feed-forward regulation of NOS2 in breast cancer progression
Published in
Proceedings of the National Academy of Sciences of the United States of America, April 2014
DOI 10.1073/pnas.1401799111
Pubmed ID
Authors

J. L. Heinecke, L. A. Ridnour, R. Y. S. Cheng, C. H. Switzer, M. M. Lizardo, C. Khanna, S. A. Glynn, S. P. Hussain, H. A. Young, S. Ambs, D. A. Wink

Abstract

Inflammation is widely recognized as an inducer of cancer progression. The inflammation-associated enzyme, inducible nitric oxide synthase (NOS2), has emerged as a candidate oncogene in estrogen receptor (ER)-negative breast cancer, and its increased expression is associated with disease aggressiveness and poor survival. Although these observations implicate NOS2 as an attractive therapeutic target, the mechanisms of both NOS2 induction in tumors and nitric oxide (NO)-driven cancer progression are not fully understood. To enhance our mechanistic understanding of NOS2 induction in tumors and its role in tumor biology, we used stimulants of NOS2 expression in ER(-) and ER(+) breast cancer cells and examined downstream NO-dependent effects. Herein, we show that up-regulation of NOS2 occurs in response to hypoxia, serum withdrawal, IFN-γ, and exogenous NO, consistent with a feed-forward regulation of NO production by the tumor microenvironment in breast cancer biology. Moreover, we found that key indicators of an aggressive cancer phenotype including increased S100 calcium binding protein A8, IL-6, IL-8, and tissue inhibitor matrix metalloproteinase-1 are up-regulated by these NOS2 stimulants, whereas inhibition of NOS2 in MDA-MB-231 breast cancer cells suppressed these markers. Moreover, NO altered cellular migration and chemoresistance of MDA-MB-231 cells to Taxol. Most notably, MDA-MB-231 tumor xenographs and cell metastases from the fat pad to the brain were significantly suppressed by NOS2 inhibition in nude mice. In summary, these results link elevated NOS2 to signals from the tumor microenvironment that arise with cancer progression and show that NO production regulates chemoresistance and metastasis of breast cancer cells.

Twitter Demographics

The data shown below were collected from the profiles of 3 tweeters 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 80 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Germany 2 3%
France 1 1%
Malaysia 1 1%
Hungary 1 1%
Mexico 1 1%
Japan 1 1%
United States 1 1%
Unknown 72 90%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 25 31%
Researcher 13 16%
Student > Master 12 15%
Student > Doctoral Student 7 9%
Professor 5 6%
Other 14 18%
Unknown 4 5%
Readers by discipline Count As %
Agricultural and Biological Sciences 23 29%
Biochemistry, Genetics and Molecular Biology 17 21%
Medicine and Dentistry 8 10%
Chemistry 8 10%
Engineering 4 5%
Other 14 18%
Unknown 6 8%

Attention Score in Context

This research output has an Altmetric Attention Score of 3. 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 29 April 2014.
All research outputs
#6,547,043
of 12,365,166 outputs
Outputs from Proceedings of the National Academy of Sciences of the United States of America
#64,715
of 77,340 outputs
Outputs of similar age
#73,319
of 197,483 outputs
Outputs of similar age from Proceedings of the National Academy of Sciences of the United States of America
#761
of 1,097 outputs
Altmetric has tracked 12,365,166 research outputs across all sources so far. This one is in the 46th percentile – i.e., 46% of other outputs scored the same or lower than it.
So far Altmetric has tracked 77,340 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 22.0. This one is in the 15th percentile – i.e., 15% 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 197,483 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 62% of its contemporaries.
We're also able to compare this research output to 1,097 others from the same source and published within six weeks on either side of this one. This one is in the 28th percentile – i.e., 28% of its contemporaries scored the same or lower than it.