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Benzylserine inhibits breast cancer cell growth by disrupting intracellular amino acid homeostasis and triggering amino acid response pathways

Overview of attention for article published in BMC Cancer, June 2018
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Title
Benzylserine inhibits breast cancer cell growth by disrupting intracellular amino acid homeostasis and triggering amino acid response pathways
Published in
BMC Cancer, June 2018
DOI 10.1186/s12885-018-4599-8
Pubmed ID
Authors

Michelle van Geldermalsen, Lake-Ee Quek, Nigel Turner, Natasha Freidman, Angel Pang, Yi Fang Guan, James R. Krycer, Renae Ryan, Qian Wang, Jeff Holst

Abstract

Cancer cells require increased levels of nutrients such as amino acids to sustain their rapid growth. In particular, leucine and glutamine have been shown to be important for growth and proliferation of some breast cancers, and therefore targeting the primary cell-surface transporters that mediate their uptake, L-type amino acid transporter 1 (LAT1) and alanine, serine, cysteine-preferring transporter 2 (ASCT2), is a potential therapeutic strategy. The ASCT2 inhibitor, benzylserine (BenSer), is also able to block LAT1 activity, thus inhibiting both leucine and glutamine uptake. We therefore aimed to investigate the effects of BenSer in breast cancer cell lines to determine whether combined LAT1 and ASCT2 inhibition could inhibit cell growth and proliferation. BenSer treatment significantly inhibited both leucine and glutamine uptake in MCF-7, HCC1806 and MDA-MB-231 breast cancer cells, causing decreased cell viability and cell cycle progression. These effects were not primarily leucine-mediated, as BenSer was more cytostatic than the LAT family inhibitor, BCH. Oocyte uptake assays with ectopically expressed amino acid transporters identified four additional targets of BenSer, and gas chromatography-mass spectrometry (GCMS) analysis of intracellular amino acid concentrations revealed that this BenSer-mediated inhibition of amino acid uptake was sufficient to disrupt multiple pathways of amino acid metabolism, causing reduced lactate production and activation of an amino acid response (AAR) through activating transcription factor 4 (ATF4). Together these data showed that BenSer blockade inhibited breast cancer cell growth and viability through disruption of intracellular amino acid homeostasis and inhibition of downstream metabolic and growth pathways.

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The data shown below were collected from the profiles of 3 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 41 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 41 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 5 12%
Student > Bachelor 5 12%
Student > Ph. D. Student 4 10%
Student > Doctoral Student 3 7%
Researcher 3 7%
Other 4 10%
Unknown 17 41%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 12 29%
Chemistry 5 12%
Medicine and Dentistry 2 5%
Pharmacology, Toxicology and Pharmaceutical Science 1 2%
Business, Management and Accounting 1 2%
Other 4 10%
Unknown 16 39%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 September 2018.
All research outputs
#14,869,034
of 23,881,329 outputs
Outputs from BMC Cancer
#3,465
of 8,483 outputs
Outputs of similar age
#188,593
of 331,060 outputs
Outputs of similar age from BMC Cancer
#71
of 139 outputs
Altmetric has tracked 23,881,329 research outputs across all sources so far. This one is in the 37th percentile – i.e., 37% of other outputs scored the same or lower than it.
So far Altmetric has tracked 8,483 research outputs from this source. They receive a mean Attention Score of 4.4. This one has gotten more attention than average, scoring higher than 59% 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 331,060 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 42nd percentile – i.e., 42% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 139 others from the same source and published within six weeks on either side of this one. This one is in the 49th percentile – i.e., 49% of its contemporaries scored the same or lower than it.