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Small Molecule-Induced Mitochondrial Disruption Directs Prostate Cancer Inhibition via Unfolded Protein Response Signaling

Overview of attention for article published in Oncotarget, July 2013
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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 (97th percentile)
  • High Attention Score compared to outputs of the same age and source (99th percentile)

Mentioned by

news
7 news outlets
patent
1 patent

Citations

dimensions_citation
21 Dimensions

Readers on

mendeley
27 Mendeley
Title
Small Molecule-Induced Mitochondrial Disruption Directs Prostate Cancer Inhibition via Unfolded Protein Response Signaling
Published in
Oncotarget, July 2013
DOI 10.18632/oncotarget.1130
Pubmed ID
Authors

Elizabeth Rico-Bautista, Wenhong Zhu, Shinichi Kitada, Suthakar Ganapathy, Eric Lau, Stan Krajewski, Joel Ramirez, Jason A. Bush, Zhimin Yuan, Dieter A. Wolf

Abstract

We previously identified SMIP004 (N-(4-butyl-2-methyl-phenyl) acetamide) as a novel inducer of cancer-cell selective apoptosis of human prostate cancer cells. SMIP004 decreased the levels of positive cell cycle regulators, upregulated cyclin-dependent kinase inhibitors, and resulted in G1 arrest, inhibition of colony formation in soft agar, and cell death. However, the mechanism of SMIP004-induced cancer cell selective apoptosis remained unknown. Here, we used chemical genomic and proteomic profiling to unravel a SMIP004-induced pro-apoptotic pathway, which initiates with disruption of mitochondrial respiration leading to oxidative stress. This, in turn, activates two pathways, one eliciting cell cycle arrest by rapidly targeting cyclin D1 for proteasomal degradation and driving the transcriptional downregulation of the androgen receptor, and a second pathway that activates pro-apoptotic signaling through MAPK activation downstream of the unfolded protein response (UPR). SMIP004 potently inhibits the growth of prostate and breast cancer xenografts in mice. Our data suggest that SMIP004, by inducing mitochondrial ROS formation, targets specific sensitivities of prostate cancer cells to redox and bioenergetic imbalances that can be exploited in cancer therapy.

Mendeley readers

The data shown below were compiled from readership statistics for 27 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 4%
Unknown 26 96%

Demographic breakdown

Readers by professional status Count As %
Researcher 8 30%
Student > Doctoral Student 4 15%
Student > Master 4 15%
Student > Ph. D. Student 4 15%
Student > Bachelor 3 11%
Other 2 7%
Unknown 2 7%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 10 37%
Agricultural and Biological Sciences 6 22%
Medicine and Dentistry 5 19%
Pharmacology, Toxicology and Pharmaceutical Science 1 4%
Computer Science 1 4%
Other 3 11%
Unknown 1 4%

Attention Score in Context

This research output has an Altmetric Attention Score of 52. 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 07 May 2015.
All research outputs
#467,261
of 16,728,998 outputs
Outputs from Oncotarget
#172
of 12,962 outputs
Outputs of similar age
#4,783
of 162,579 outputs
Outputs of similar age from Oncotarget
#1
of 15 outputs
Altmetric has tracked 16,728,998 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 97th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 12,962 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 162,579 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 97% of its contemporaries.
We're also able to compare this research output to 15 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 99% of its contemporaries.