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Revealing Different Roles of the mTOR-Targets S6K1 and S6K2 in Breast Cancer by Expression Profiling and Structural Analysis

Overview of attention for article published in PLoS ONE, December 2015
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (84th percentile)
  • High Attention Score compared to outputs of the same age and source (82nd percentile)

Mentioned by

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1 blog
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2 tweeters

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15 Mendeley
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Title
Revealing Different Roles of the mTOR-Targets S6K1 and S6K2 in Breast Cancer by Expression Profiling and Structural Analysis
Published in
PLoS ONE, December 2015
DOI 10.1371/journal.pone.0145013
Pubmed ID
Authors

Elin Karlsson, Ivana Magić, Josefine Bostner, Christine Dyrager, Fredrik Lysholm, Anna-Lotta Hallbeck, Olle Stål, Patrik Lundström

Abstract

The AKT/mTORC1/S6K pathway is frequently overstimulated in breast cancer, constituting a promising therapeutic target. The benefit from mTOR inhibitors varies, likely as a consequence of tumour heterogeneity, and upregulation of several compensatory feed-back mechanisms. The mTORC1 downstream effectors S6K1, S6K2, and 4EBP1 are amplified and overexpressed in breast cancer, associated with a poor outcome and divergent endocrine treatment benefit. S6K1 and S6K2 share high sequence homology, but evidence of partly distinct biological functions is emerging. The aim of this work was to explore possible different roles and treatment target potentials of S6K1 and S6K2 in breast cancer. Whole-genome expression profiles were compared for breast tumours expressing high levels of S6K1, S6K2 or 4EBP1, using public datasets, as well as after in vitro siRNA downregulation of S6K1 and/or S6K2 in ZR751 breast cancer cells. In silico homology modelling of the S6K2 kinase domain was used to evaluate its possible structural divergences to S6K1. Genome expression profiles were highly different in S6K1 and S6K2 high tumours, whereas S6K2 and 4EBP1 profiles showed significant overlaps, both correlated to genes involved in cell cycle progression, among these the master regulator E2F1. S6K2 and 4EBP1 were inversely associated with IGF1 levels, and their prognostic value was shown to be restricted to tumours positive for IGFR and/or HER2. In vitro, S6K1 and S6K2 silencing resulted in upregulation of genes in the mTORC1 and mTORC2 complexes. Isoform-specific silencing also showed distinct patterns, e.g. S6K2 downregulation lead to upregulation of several cell cycle associated genes. Structural analyses of the S6K2 kinase domain showed unique structure patterns, deviating from those of S6K1, facilitating the development of isoform-specific inhibitors. Our data support emerging proposals of distinct biological features of S6K1 and S6K2, suggesting their importance as separate oncogenes and clinical markers, where specific targeting in different breast cancer subtypes could facilitate further individualised therapies.

Twitter Demographics

The data shown below were collected from the profiles of 2 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 15 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 15 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 5 33%
Researcher 3 20%
Student > Bachelor 2 13%
Student > Ph. D. Student 2 13%
Student > Postgraduate 1 7%
Other 2 13%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 6 40%
Agricultural and Biological Sciences 3 20%
Unspecified 2 13%
Business, Management and Accounting 1 7%
Nursing and Health Professions 1 7%
Other 2 13%

Attention Score in Context

This research output has an Altmetric Attention Score of 9. 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 25 December 2015.
All research outputs
#803,077
of 6,865,651 outputs
Outputs from PLoS ONE
#18,051
of 101,744 outputs
Outputs of similar age
#45,489
of 295,814 outputs
Outputs of similar age from PLoS ONE
#870
of 4,933 outputs
Altmetric has tracked 6,865,651 research outputs across all sources so far. Compared to these this one has done well and is in the 88th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 101,744 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.9. This one has done well, scoring higher than 82% 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 295,814 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 84% of its contemporaries.
We're also able to compare this research output to 4,933 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 82% of its contemporaries.