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AKT signalling is required for ribosomal RNA synthesis and progression of Eμ‐Myc B‐cell lymphoma in vivo

Overview of attention for article published in FEBS Journal, February 2013
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Title
AKT signalling is required for ribosomal RNA synthesis and progression of Eμ‐Myc B‐cell lymphoma in vivo
Published in
FEBS Journal, February 2013
DOI 10.1111/febs.12135
Pubmed ID
Authors

Jennifer R. Devlin, Katherine M. Hannan, Pui Y. Ng, Megan J. Bywater, Jake Shortt, Carleen Cullinane, Grant A. McArthur, Ricky W. Johnstone, Ross D. Hannan, Richard B. Pearson

Abstract

The dysregulation of PI3K/AKT/mTORC1 signalling and/or hyperactivation of MYC are observed in a high proportion of human cancers, and together they form a 'super signalling' network mediating malignancy. A fundamental downstream action of this signalling network is up-regulation of ribosome biogenesis and subsequent alterations in the patterns of translation and increased protein synthesis, which are thought to be critical for AKT/MYC-driven oncogenesis. We have demonstrated that AKT and MYC cooperate to drive ribosomal DNA (rDNA) transcription and ribosome biogenesis, with AKT being essential for rDNA transcription and in vitro survival of lymphoma cells isolated from a MYC-driven model of B-cell lymphoma (Eμ-Myc) [Chan JC et al., (2011) Science Signalling 4, ra56]. Here we show that the allosteric AKT inhibitor MK-2206 rapidly and potently antagonizes rDNA transcription in Eμ-Myc B-cell lymphomas in vivo, and this is associated with a rapid reduction in indicators of disease burden, including spleen weight and the abundance of tumour cells in both the circulation and lymph nodes. Extended treatment of tumour-bearing mice with MK-2206 resulted in a significant delay in disease progression, associated with increased B-cell lymphoma apoptosis. Our findings suggest that malignant diseases characterized by unrestrained ribosome biogenesis may be vulnerable to therapeutic strategies that target the PI3K/AKT/mTORC1/MYC growth control network.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 31 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 2 6%
United Kingdom 1 3%
Unknown 28 90%

Demographic breakdown

Readers by professional status Count As %
Researcher 8 26%
Student > Ph. D. Student 4 13%
Student > Bachelor 3 10%
Student > Doctoral Student 2 6%
Librarian 2 6%
Other 8 26%
Unknown 4 13%
Readers by discipline Count As %
Agricultural and Biological Sciences 13 42%
Biochemistry, Genetics and Molecular Biology 6 19%
Medicine and Dentistry 4 13%
Immunology and Microbiology 1 3%
Business, Management and Accounting 1 3%
Other 2 6%
Unknown 4 13%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 13 February 2013.
All research outputs
#19,962,154
of 25,394,764 outputs
Outputs from FEBS Journal
#10,719
of 12,265 outputs
Outputs of similar age
#225,726
of 296,727 outputs
Outputs of similar age from FEBS Journal
#114
of 172 outputs
Altmetric has tracked 25,394,764 research outputs across all sources so far. This one is in the 18th percentile – i.e., 18% of other outputs scored the same or lower than it.
So far Altmetric has tracked 12,265 research outputs from this source. They receive a mean Attention Score of 4.8. This one is in the 10th percentile – i.e., 10% 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 296,727 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 21st percentile – i.e., 21% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 172 others from the same source and published within six weeks on either side of this one. This one is in the 33rd percentile – i.e., 33% of its contemporaries scored the same or lower than it.