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The metabolic function of cyclin D3–CDK6 kinase in cancer cell survival

Overview of attention for article published in Nature, June 2017
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  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (95th percentile)
  • Average Attention Score compared to outputs of the same age and source

Citations

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267 Dimensions

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361 Mendeley
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Title
The metabolic function of cyclin D3–CDK6 kinase in cancer cell survival
Published in
Nature, June 2017
DOI 10.1038/nature22797
Pubmed ID
Authors

Haizhen Wang, Brandon N. Nicolay, Joel M. Chick, Xueliang Gao, Yan Geng, Hong Ren, Hui Gao, Guizhi Yang, Juliet A. Williams, Jan M. Suski, Mark A. Keibler, Ewa Sicinska, Ulrike Gerdemann, W. Nicholas Haining, Thomas M. Roberts, Kornelia Polyak, Steven P. Gygi, Nicholas J. Dyson, Piotr Sicinski

Abstract

D-type cyclins (D1, D2 and D3) and their associated cyclin-dependent kinases (CDK4 and CDK6) are components of the core cell cycle machinery that drives cell proliferation. Inhibitors of CDK4 and CDK6 are currently being tested in clinical trials for patients with several cancer types, with promising results. Here, using human cancer cells and patient-derived xenografts in mice, we show that the cyclin D3-CDK6 kinase phosphorylates and inhibits the catalytic activity of two key enzymes in the glycolytic pathway, 6-phosphofructokinase and pyruvate kinase M2. This re-directs the glycolytic intermediates into the pentose phosphate (PPP) and serine pathways. Inhibition of cyclin D3-CDK6 in tumour cells reduces flow through the PPP and serine pathways, thereby depleting the antioxidants NADPH and glutathione. This, in turn, increases the levels of reactive oxygen species and causes apoptosis of tumour cells. The pro-survival function of cyclin D-associated kinase operates in tumours expressing high levels of cyclin D3-CDK6 complexes. We propose that measuring the levels of cyclin D3-CDK6 in human cancers might help to identify tumour subsets that undergo cell death and tumour regression upon inhibition of CDK4 and CDK6. Cyclin D3-CDK6, through its ability to link cell cycle and cell metabolism, represents a particularly powerful oncoprotein that affects cancer cells at several levels, and this property can be exploited for anti-cancer therapy.

X Demographics

X Demographics

The data shown below were collected from the profiles of 56 X users 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 361 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Germany 1 <1%
Switzerland 1 <1%
Netherlands 1 <1%
Austria 1 <1%
United Kingdom 1 <1%
Unknown 356 99%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 86 24%
Researcher 60 17%
Student > Bachelor 41 11%
Student > Master 34 9%
Professor > Associate Professor 17 5%
Other 54 15%
Unknown 69 19%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 120 33%
Agricultural and Biological Sciences 65 18%
Medicine and Dentistry 36 10%
Immunology and Microbiology 16 4%
Chemistry 10 3%
Other 40 11%
Unknown 74 20%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 62. 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 May 2021.
All research outputs
#686,066
of 25,382,360 outputs
Outputs from Nature
#26,656
of 97,623 outputs
Outputs of similar age
#14,095
of 319,507 outputs
Outputs of similar age from Nature
#495
of 814 outputs
Altmetric has tracked 25,382,360 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 97th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 97,623 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 102.3. This one has gotten more attention than average, scoring higher than 72% 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 319,507 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 95% of its contemporaries.
We're also able to compare this research output to 814 others from the same source and published within six weeks on either side of this one. This one is in the 39th percentile – i.e., 39% of its contemporaries scored the same or lower than it.