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Estrone Sulfate Transport and Steroid Sulfatase Activity in Colorectal Cancer: Implications for Hormone Replacement Therapy

Overview of attention for article published in Frontiers in Pharmacology, March 2017
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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (70th percentile)
  • High Attention Score compared to outputs of the same age and source (82nd percentile)

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Title
Estrone Sulfate Transport and Steroid Sulfatase Activity in Colorectal Cancer: Implications for Hormone Replacement Therapy
Published in
Frontiers in Pharmacology, March 2017
DOI 10.3389/fphar.2017.00103
Pubmed ID
Authors

Lorna C. Gilligan, Ali Gondal, Vivien Tang, Maryam T. Hussain, Anastasia Arvaniti, Anne-Marie Hewitt, Paul A. Foster

Abstract

Hormone replacement therapy (HRT) affects the incidence and potential progression of colorectal cancer (CRC). As HRT primarily consists of estrone sulfate (E1S), understanding whether this conjugated estrogen is transported and metabolized in CRC will define its potential effect in this malignancy. Here, we show that a panel of CRC cell lines (Colo205, Caco2, HCT116, HT-29) have steroid sulfatase (STS) activity, and thus can hydrolyze E1S. STS activity is significantly higher in CRC cell lysate, suggesting the importance of E1S transport in intracellular STS substrate availability. As E1S transport is regulated by the expression pattern of certain solute carrier organic anion transporter polypeptides, we show that in CRC OATP4A1 is the most abundantly expressed transporter. All four CRC cell lines rapidly transported E1S into cells, with this effect significantly inhibited by the competitive OATP inhibitor BSP. Transient knockdown of OATP4A1 significantly disrupted E1S uptake. Examination of estrogen receptor status showed ERα was present in Colo205 and Caco2 cells. None of the cells expressed ERβ. Intriguingly, HCT116 and HT29 cells strongly expressed the G protein coupled estrogen receptor (GPER), and that stimulation of this receptor with estradiol (E2) and G1, a GPER agonist, significantly (p < 0.01) increased STS activity. Furthermore, tamoxifen and fulvestrant, known GPER agonist, also increased CRC STS activity, with this effect inhibited by the GPER antagonist G15. These results suggest that CRC can take up and hydrolyze E1S, and that subsequent GPER stimulation increases STS activity in a potentially novel positive feedback loop. As elevated STS expression is associated with poor prognosis in CRC, these results suggest HRT, tamoxifen and fulvestrant may negatively impact CRC patient outcomes.

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X Demographics

The data shown below were collected from the profiles of 5 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 19 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 19 100%

Demographic breakdown

Readers by professional status Count As %
Student > Postgraduate 3 16%
Other 2 11%
Student > Bachelor 2 11%
Student > Master 2 11%
Student > Ph. D. Student 1 5%
Other 3 16%
Unknown 6 32%
Readers by discipline Count As %
Medicine and Dentistry 5 26%
Biochemistry, Genetics and Molecular Biology 4 21%
Pharmacology, Toxicology and Pharmaceutical Science 3 16%
Chemistry 1 5%
Unknown 6 32%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 6. 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 15 December 2018.
All research outputs
#5,548,754
of 22,955,959 outputs
Outputs from Frontiers in Pharmacology
#2,153
of 16,230 outputs
Outputs of similar age
#88,976
of 307,986 outputs
Outputs of similar age from Frontiers in Pharmacology
#34
of 198 outputs
Altmetric has tracked 22,955,959 research outputs across all sources so far. Compared to these this one has done well and is in the 75th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 16,230 research outputs from this source. They receive a mean Attention Score of 5.0. This one has done well, scoring higher than 86% 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 307,986 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 70% of its contemporaries.
We're also able to compare this research output to 198 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 82% of its contemporaries.