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X Demographics
Mendeley readers
Attention Score in Context
| Title |
Withaferin A Alters Intermediate Filament Organization, Cell Shape and Behavior
|
|---|---|
| Published in |
PLOS ONE, June 2012
|
| DOI | 10.1371/journal.pone.0039065 |
| Pubmed ID | |
| Authors |
Boris Grin, Saleemulla Mahammad, Tatjana Wedig, Megan M. Cleland, Lester Tsai, Harald Herrmann, Robert D. Goldman |
| Abstract |
Withaferin A (WFA) is a steroidal lactone present in Withania somnifera which has been shown in vitro to bind to the intermediate filament protein, vimentin. Based upon its affinity for vimentin, it has been proposed that WFA can be used as an anti-tumor agent to target metastatic cells which up-regulate vimentin expression. We show that WFA treatment of human fibroblasts rapidly reorganizes vimentin intermediate filaments (VIF) into a perinuclear aggregate. This reorganization is dose dependent and is accompanied by a change in cell shape, decreased motility and an increase in vimentin phosphorylation at serine-38. Furthermore, vimentin lacking cysteine-328, the proposed WFA binding site, remains sensitive to WFA demonstrating that this site is not required for its cellular effects. Using analytical ultracentrifugation, viscometry, electron microscopy and sedimentation assays we show that WFA has no effect on VIF assembly in vitro. Furthermore, WFA is not specific for vimentin as it disrupts the cellular organization and induces perinuclear aggregates of several other IF networks comprised of peripherin, neurofilament-triplet protein, and keratin. In cells co-expressing keratin IF and VIF, the former are significantly less sensitive to WFA with respect to inducing perinuclear aggregates. The organization of microtubules and actin/microfilaments is also affected by WFA. Microtubules become wavier and sparser and the number of stress fibers appears to increase. Following 24 hrs of exposure to doses of WFA that alter VIF organization and motility, cells undergo apoptosis. Lower doses of the drug do not kill cells but cause them to senesce. In light of our findings that WFA affects multiple IF systems, which are expressed in many tissues of the body, caution is warranted in its use as an anti-cancer agent, since it may have debilitating organism-wide effects. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 108 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 2 | 2% |
| Finland | 1 | <1% |
| France | 1 | <1% |
| Unknown | 104 | 96% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 30 | 28% |
| Researcher | 18 | 17% |
| Professor > Associate Professor | 9 | 8% |
| Student > Bachelor | 7 | 6% |
| Student > Master | 7 | 6% |
| Other | 14 | 13% |
| Unknown | 23 | 21% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 32 | 30% |
| Biochemistry, Genetics and Molecular Biology | 20 | 19% |
| Engineering | 7 | 6% |
| Medicine and Dentistry | 6 | 6% |
| Immunology and Microbiology | 5 | 5% |
| Other | 12 | 11% |
| Unknown | 26 | 24% |
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 15 June 2012.
All research outputs
#20,159,700
of 22,668,244 outputs
Outputs from PLOS ONE
#172,674
of 193,511 outputs
Outputs of similar age
#150,065
of 166,052 outputs
Outputs of similar age from PLOS ONE
#3,525
of 3,847 outputs
Altmetric has tracked 22,668,244 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 193,511 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.0. This one is in the 1st percentile – i.e., 1% 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 166,052 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 3,847 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.