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A novel phosphatidylinositol 3-kinase (PI3K) inhibitor directs a potent FOXO-dependent, p53-independent cell cycle arrest phenotype characterized by the differential induction of a subset of FOXO-regul…

Overview of attention for article published in Breast Cancer Research, December 2014
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About this Attention Score

  • Above-average Attention Score compared to outputs of the same age (60th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (58th percentile)

Mentioned by

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1 tweeter
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2 Facebook pages
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1 research highlight platform

Citations

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25 Dimensions

Readers on

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37 Mendeley
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Title
A novel phosphatidylinositol 3-kinase (PI3K) inhibitor directs a potent FOXO-dependent, p53-independent cell cycle arrest phenotype characterized by the differential induction of a subset of FOXO-regulated genes
Published in
Breast Cancer Research, December 2014
DOI 10.1186/s13058-014-0482-y
Pubmed ID
Authors

Richard Hill, Ravi Kiran Reddy Kalathur, Sergio Callejas, Laura Colaço, Ricardo Brandão, Beatriz Serelde, Antonio Cebriá, Carmen Blanco-Aparicio, Joaquín Pastor, Matthias Futschik, Ana Dopazo, Wolfgang Link

Abstract

IntroductionThe activation of the phosphoinositide 3-kinase (PI3K)/AKT signalling pathway is one the most frequent genetic events in breast cancer, consequently the development of PI3K inhibitors has attracted much attention. Here we evaluate the effect of PI3K inhibition on global gene expression in breast cancer cells.MethodsWe used a range of methodologies that include in silico compound analysis, in vitro kinase assays, cell invasion assays, proliferation assays, genome wide transcription studies (Agilent Technologies full genome arrays), gene set enrichment analysis, quantitative real time PCR, immunoblotting in addition to chromatin-immunoprecipitation.ResultsWe defined the physico-chemical and the biological properties of ETP-45658, a novel potent PI3K inhibitor. We demonstrated that ETP-45658 potently inhibited cell proliferation within a broad range of human cancer cells, most potently suppressing the growth of breast cancer cells via inhibiting cell cycle. We show that this response is Forkhead box O (FOXO) protein-dependent and p53-independent. Our genome-wide microarray analysis revealed that the cell cycle was the most affected biological process after exposure to ETP-45658 (or our control PI3K inhibitor PI-103), that despite the multiple transcription factors that are regulated by the PI3K/AKT signalling cascade, only the binding sites for FOXO transcription factors were significantly enriched and only a subset of all FOXO-dependent genes were induced. This disparity in gene transcription was not due to differential FOXO promoter recruitment.ConclusionsThe constitutive activation of PI3Ks and thus the exclusion of FOXO transcription factors from the nucleus is a key feature of breast cancer. Our results presented here highlight that PI3K inhibition activates specific FOXO-dependent genes that mediate cell cycle arrest in breast cancer cells.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter 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 37 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Spain 1 3%
Unknown 36 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 8 22%
Researcher 8 22%
Student > Bachelor 8 22%
Student > Doctoral Student 2 5%
Student > Master 2 5%
Other 5 14%
Unknown 4 11%
Readers by discipline Count As %
Agricultural and Biological Sciences 10 27%
Biochemistry, Genetics and Molecular Biology 10 27%
Medicine and Dentistry 6 16%
Pharmacology, Toxicology and Pharmaceutical Science 3 8%
Nursing and Health Professions 1 3%
Other 2 5%
Unknown 5 14%

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 28 April 2016.
All research outputs
#6,921,678
of 12,786,466 outputs
Outputs from Breast Cancer Research
#853
of 1,448 outputs
Outputs of similar age
#109,986
of 293,106 outputs
Outputs of similar age from Breast Cancer Research
#14
of 39 outputs
Altmetric has tracked 12,786,466 research outputs across all sources so far. This one is in the 44th percentile – i.e., 44% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,448 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.0. This one is in the 38th percentile – i.e., 38% 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 293,106 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 60% of its contemporaries.
We're also able to compare this research output to 39 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 58% of its contemporaries.