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Fatty acid synthase overexpression: target for therapy and reversal of chemoresistance in ovarian cancer

Overview of attention for article published in Journal of Translational Medicine, May 2015
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Title
Fatty acid synthase overexpression: target for therapy and reversal of chemoresistance in ovarian cancer
Published in
Journal of Translational Medicine, May 2015
DOI 10.1186/s12967-015-0511-3
Pubmed ID
Authors

Dirk O Bauerschlag, Nicolai Maass, Peter Leonhardt, Frederik A Verburg, Ulrich Pecks, Felix Zeppernick, Agnieszka Morgenroth, Felix M Mottaghy, Rene Tolba, Ivo Meinhold-Heerlein, Karen Bräutigam

Abstract

Fatty acid synthase (FASN) is crucial to de novo long-chain fatty acid synthesis, needed to meet cancer cells' increased demands for membrane, energy, and protein production. We investigated FASN overexpression as a therapeutic and chemosensitization target in ovarian cancer tissue, cell lines, and primary cell cultures. FASN expression at mRNA and protein levels was determined by quantitative real-time polymerase chain reaction and immunoblotting and immunohistochemistry, respectively. FASN inhibition's impact on cell viability, apoptosis, and fatty acid metabolism was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide assay, cell death detection enzyme-linked immunosorbent assay, immunoblotting, and (18) F-fluoromethylcholine uptake measurement, respectively. Relative to that in healthy fallopian tube tissue, tumor tissues had 1.8-fold average FASN protein overexpression; cell lines and primary cultures had 11-fold-100-fold mRNA and protein overexpression. In most samples, the FASN inhibitor cerulenin markedly decreased FASN expression and cell viability and induced apoptosis. Unlike concomitant administration, sequential cerulenin/cisplatin treatment reduced cisplatin's half maximal inhibitory concentration profoundly (up to 54%) in a cisplatin-resistant cell line, suggesting platinum (re)sensitization. Cisplatin-resistant cells displayed lower (18) F-fluoro-methylcholine uptake than did cisplatin-sensitive cells, suggesting that metabolic imaging might help guide therapy. FASN inhibition induced apoptosis in chemosensitive and platinum-resistant ovarian cancer cells and may reverse cisplatin resistance.

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 68 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Iran, Islamic Republic of 1 1%
Unknown 67 99%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 15 22%
Researcher 14 21%
Student > Master 7 10%
Student > Bachelor 6 9%
Student > Doctoral Student 3 4%
Other 9 13%
Unknown 14 21%
Readers by discipline Count As %
Medicine and Dentistry 15 22%
Biochemistry, Genetics and Molecular Biology 15 22%
Agricultural and Biological Sciences 13 19%
Immunology and Microbiology 3 4%
Unspecified 2 3%
Other 6 9%
Unknown 14 21%

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 14 May 2015.
All research outputs
#11,068,876
of 12,450,491 outputs
Outputs from Journal of Translational Medicine
#2,389
of 2,446 outputs
Outputs of similar age
#187,664
of 226,263 outputs
Outputs of similar age from Journal of Translational Medicine
#2
of 2 outputs
Altmetric has tracked 12,450,491 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,446 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.2. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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