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Functional, chemical genomic, and super-enhancer screening identify sensitivity to cyclin D1/CDK4 pathway inhibition in Ewing sarcoma

Overview of attention for article published in Oncotarget, August 2015
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About this Attention Score

  • Good Attention Score compared to outputs of the same age (66th percentile)
  • Good Attention Score compared to outputs of the same age and source (75th percentile)

Mentioned by

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1 X user
wikipedia
1 Wikipedia page

Citations

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68 Dimensions

Readers on

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83 Mendeley
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Title
Functional, chemical genomic, and super-enhancer screening identify sensitivity to cyclin D1/CDK4 pathway inhibition in Ewing sarcoma
Published in
Oncotarget, August 2015
DOI 10.18632/oncotarget.4903
Pubmed ID
Authors

Alyssa L. Kennedy, Mounica Vallurupalli, Liying Chen, Brian Crompton, Glenn Cowley, Francisca Vazquez, Barbara A. Weir, Aviad Tsherniak, Sudha Parasuraman, Sunkyu Kim, Gabriela Alexe, Kimberly Stegmaier

Abstract

Ewing sarcoma is an aggressive bone and soft tissue tumor in children and adolescents, with treatment remaining a clinical challenge. This disease is mediated by somatic chromosomal translocations of the EWS gene and a gene encoding an ETS transcription factor, most commonly, FLI1. While direct targeting of aberrant transcription factors remains a pharmacological challenge, identification of dependencies incurred by EWS/FLI1 expression would offer a new therapeutic avenue. We used a combination of super-enhancer profiling, near-whole genome shRNA-based and small-molecule screening to identify cyclin D1 and CDK4 as Ewing sarcoma-selective dependencies. We revealed that super-enhancers mark Ewing sarcoma specific expression signatures and EWS/FLI1 target genes in human Ewing sarcoma cell lines. Particularly, a super-enhancer regulates cyclin D1 and promotes its expression in Ewing sarcoma. We demonstrated that Ewing sarcoma cells require CDK4 and cyclin D1 for survival and anchorage-independent growth. Additionally, pharmacologic inhibition of CDK4 with selective CDK4/6 inhibitors led to cytostasis and cell death of Ewing sarcoma cell lines in vitro and growth delay in an in vivo Ewing sarcoma xenograft model. These results demonstrated a dependency in Ewing sarcoma on CDK4 and cyclin D1 and support exploration of CDK4/6 inhibitors as a therapeutic approach for patients with this disease.

X Demographics

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.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 83 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Spain 1 1%
United States 1 1%
China 1 1%
Austria 1 1%
Unknown 79 95%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 18 22%
Researcher 14 17%
Student > Bachelor 6 7%
Student > Master 5 6%
Student > Doctoral Student 4 5%
Other 11 13%
Unknown 25 30%
Readers by discipline Count As %
Agricultural and Biological Sciences 21 25%
Biochemistry, Genetics and Molecular Biology 16 19%
Medicine and Dentistry 14 17%
Psychology 3 4%
Immunology and Microbiology 2 2%
Other 1 1%
Unknown 26 31%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 4. 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 04 August 2016.
All research outputs
#7,233,951
of 22,862,742 outputs
Outputs from Oncotarget
#3,330
of 14,326 outputs
Outputs of similar age
#85,762
of 266,243 outputs
Outputs of similar age from Oncotarget
#129
of 614 outputs
Altmetric has tracked 22,862,742 research outputs across all sources so far. This one has received more attention than most of these and is in the 67th percentile.
So far Altmetric has tracked 14,326 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.5. This one has gotten more attention than average, scoring higher than 74% 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 266,243 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 66% of its contemporaries.
We're also able to compare this research output to 614 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 75% of its contemporaries.