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Oncotarget

Article Metrics

Lipid catabolism inhibition sensitizes prostate cancer cells to antiandrogen blockade

Overview of attention for article published in Oncotarget, April 2017
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (93rd percentile)
  • High Attention Score compared to outputs of the same age and source (98th percentile)

Mentioned by

news
3 news outlets
twitter
31 tweeters
facebook
1 Facebook page

Citations

dimensions_citation
6 Dimensions

Readers on

mendeley
43 Mendeley
Title
Lipid catabolism inhibition sensitizes prostate cancer cells to antiandrogen blockade
Published in
Oncotarget, April 2017
DOI 10.18632/oncotarget.17359
Pubmed ID
Authors

Thomas W. Flaig, Maren Salzmann-Sullivan, Lih-Jen Su, Zhiyong Zhang, Molishree Joshi, Miguel A. Gijón, Jihye Kim, John J. Arcaroli, Adrie Van Bokhoven, M. Scott Lucia, Francisco G. La Rosa, Isabel R. Schlaepfer

Abstract

Prostate cancer (PCa) is the most common malignancy among Western men and the second leading-cause of cancer related deaths. For men who develop metastatic castration resistant PCa (mCRPC), survival is limited, making the identification of novel therapies for mCRPC critical. We have found that deficient lipid oxidation via carnitine palmitoyltransferase (CPT1) results in decreased growth and invasion, underscoring the role of lipid oxidation to fuel PCa growth. Using immunohistochemistry we have found that the CPT1A isoform is abundant in PCa compared to benign tissue (n=39, p<0.001) especially in those with high-grade tumors. Since lipid oxidation is stimulated by androgens, we have evaluated the synergistic effects of combining CPT1A inhibition and anti-androgen therapy. Mechanistically, we have found that decreased CPT1A expression is associated with decreased AKT content and activation, likely driven by a breakdown of membrane phospholipids and activation of the INPP5K phosphatase. This results in increased androgen receptor (AR) action and increased sensitivity to the anti-androgen enzalutamide. To better understand the clinical implications of these findings, we have evaluated fat oxidation inhibitors (etomoxir, ranolazine and perhexiline) in combination with enzalutamide in PCa cell models. We have observed a robust growth inhibitory effect of the combinations, including in enzalutamide-resistant cells and mouse TRAMPC1 cells, a more neuroendocrine PCa model. Lastly, using a xenograft mouse model, we have observed decreased tumor growth with a systemic combination treatment of enzalutamide and ranolazine. In conclusion, our results show that improved anti-cancer efficacy can be achieved by co-targeting the AR axis and fat oxidation via CPT1A, which may have clinical implications, especially in the mCRPC setting.

Twitter Demographics

The data shown below were collected from the profiles of 31 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 43 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 43 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 10 23%
Student > Ph. D. Student 7 16%
Student > Bachelor 7 16%
Student > Master 4 9%
Professor > Associate Professor 3 7%
Other 4 9%
Unknown 8 19%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 15 35%
Medicine and Dentistry 8 19%
Agricultural and Biological Sciences 4 9%
Chemistry 4 9%
Computer Science 1 2%
Other 2 5%
Unknown 9 21%

Attention Score in Context

This research output has an Altmetric Attention Score of 40. 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 29 August 2017.
All research outputs
#581,670
of 16,256,075 outputs
Outputs from Oncotarget
#237
of 12,881 outputs
Outputs of similar age
#17,188
of 269,474 outputs
Outputs of similar age from Oncotarget
#14
of 963 outputs
Altmetric has tracked 16,256,075 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 96th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 12,881 research outputs from this source. They receive a mean Attention Score of 4.2. This one has done particularly well, scoring higher than 98% 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 269,474 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 93% of its contemporaries.
We're also able to compare this research output to 963 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 98% of its contemporaries.