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Zinc ion dyshomeostasis increases resistance of prostate cancer cells to oxidative stress via upregulation of HIF1α

Overview of attention for article published in Oncotarget, January 2018
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Title
Zinc ion dyshomeostasis increases resistance of prostate cancer cells to oxidative stress via upregulation of HIF1α
Published in
Oncotarget, January 2018
DOI 10.18632/oncotarget.23893
Pubmed ID
Authors

David Wetherell, Graham S. Baldwin, Arthur Shulkes, Damien Bolton, Joseph Ischia, Oneel Patel

Abstract

Zinc ions (Zn2+) are known to influence cell survival and proliferation. However the homeostatic regulation of Zn2+and their role in prostate cancer (PC) progression is poorly understood. Therefore the subcellular distribution and uptake of Zn2+in PC cells were investigated. Inductively coupled plasma mass spectroscopy and fluorescent microscopy with the Zn2+-specific fluorescent probe FluoZin-3 were used to quantify total andfreeZn2+, respectively, in the normal prostate epithelial cell line (PNT1A) and three human PC cell lines (PC3, DU145 and LNCaP). The effects of Zn2+treatment on proliferation and survival were measuredin vitrousing MTT assays andin vivousing mouse xenografts. The ability of Zn2+to protect against oxidative stress via a HIF1α-dependent mechanism was investigated using a HIF1α knock-down PC3 model. Our results demonstrate that the total Zn2+concentration in normal PNT1A and PC cells is similar, but PC3 cells contain significantly higher free Zn2+than PNT1A cells (p< 0.01). PNT1A cells can survive better in the presence of high concentrations of Zn2+than PC3 cells. Exposure to 10 µM Zn2+over 72 hours significantly reduces PC3 cell proliferationin vitrobut notin vivo. Zn2+increases PC3 cell survival up to 2.3-fold under oxidative stress, and this protective effect is not seen in PNT1A cells or in a HIF1α-KD PC3 cell model. A state of Zn2+dyshomeostasis exists in PC. HIF1α is an integral component of a Zn2+-dependent protective mechanism present in PC3 cells. This pathway may be clinically significant through its contribution to castrate-resistant PC survival.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 17 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 17 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 5 29%
Student > Ph. D. Student 3 18%
Student > Doctoral Student 2 12%
Student > Bachelor 1 6%
Professor 1 6%
Other 2 12%
Unknown 3 18%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 5 29%
Medicine and Dentistry 3 18%
Immunology and Microbiology 2 12%
Chemical Engineering 1 6%
Earth and Planetary Sciences 1 6%
Other 1 6%
Unknown 4 24%
Attention Score in Context

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 06 January 2018.
All research outputs
#15,487,739
of 23,015,156 outputs
Outputs from Oncotarget
#6,689
of 14,344 outputs
Outputs of similar age
#270,047
of 442,518 outputs
Outputs of similar age from Oncotarget
#332
of 767 outputs
Altmetric has tracked 23,015,156 research outputs across all sources so far. This one is in the 22nd percentile – i.e., 22% of other outputs scored the same or lower than it.
So far Altmetric has tracked 14,344 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.6. This one is in the 46th percentile – i.e., 46% of its peers scored the same or lower than it.
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 442,518 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 29th percentile – i.e., 29% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 767 others from the same source and published within six weeks on either side of this one. This one is in the 46th percentile – i.e., 46% of its contemporaries scored the same or lower than it.