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NZ28-induced inhibition of HSF1, SP1 and NF-κB triggers the loss of the natural killer cell-activating ligands MICA/B on human tumor cells

Overview of attention for article published in Cancer Immunology, Immunotherapy, February 2015
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4 tweeters

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24 Mendeley
Title
NZ28-induced inhibition of HSF1, SP1 and NF-κB triggers the loss of the natural killer cell-activating ligands MICA/B on human tumor cells
Published in
Cancer Immunology, Immunotherapy, February 2015
DOI 10.1007/s00262-015-1665-9
Pubmed ID
Authors

Daniela Schilling, Annett Kühnel, Fabian Tetzlaff, Sarah Konrad, Gabriele Multhoff

Abstract

The activity of natural killer (NK) cells is regulated by activating and inhibiting receptors, whereby the C-type lectin natural killer group 2D (NKG2D) receptor serves as the major activating receptor on NK cells which recognizes major histocompatibility class I chain-related proteins A and B (MICA/B). The MICA/B expression has been described to be regulated by the transcription factor heat shock factor 1 (HSF1). Inhibition of heat shock protein 90 (Hsp90) is known to induce the heat shock response via activation of HSF1 which is associated with tumor development, metastasis and therapy resistance and also with an increased susceptibility to NK cell-mediated lysis. Therefore, we compared the effects of Hsp90 inhibitor NVP-AUY922, HSF1 inhibitor NZ28 and HSF1 knockdown on the sensitivity of lung (H1339) and breast (MDA-MB-231, T47D) cancer cells to NK cell-mediated cytotoxicity and the expression of the NKG2D ligands MICA/B. Although NVP-AUY922 activates HSF1, neither the MICA/B surface density on tumor cells nor their susceptibility to NK cell-mediated lysis was affected. A single knockdown of HSF1 by shRNA decreased the surface expression of MICB but not that of MICA, and thereby, the NK cell-mediated lysis was only partially blocked. In contrast, NZ28 completely blocked the MICA/B membrane expression on tumor cells and thereby strongly inhibited the NK cell-mediated cytotoxicity. This effect might be explained by a simultaneous inhibition of the transcription factors HSF1, Sp1 and NF-κB by NZ28. These findings suggest that new anticancer therapeutics should be investigated with respect to their effects on the innate immune system.

Twitter Demographics

The data shown below were collected from the profiles of 4 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 24 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 4%
Canada 1 4%
Unknown 22 92%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 25%
Researcher 4 17%
Unspecified 4 17%
Student > Master 4 17%
Student > Bachelor 2 8%
Other 4 17%
Readers by discipline Count As %
Agricultural and Biological Sciences 6 25%
Medicine and Dentistry 5 21%
Unspecified 5 21%
Immunology and Microbiology 3 13%
Biochemistry, Genetics and Molecular Biology 3 13%
Other 2 8%

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 09 August 2015.
All research outputs
#7,634,850
of 12,216,428 outputs
Outputs from Cancer Immunology, Immunotherapy
#1,437
of 1,811 outputs
Outputs of similar age
#127,214
of 230,682 outputs
Outputs of similar age from Cancer Immunology, Immunotherapy
#16
of 35 outputs
Altmetric has tracked 12,216,428 research outputs across all sources so far. This one is in the 23rd percentile – i.e., 23% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,811 research outputs from this source. They receive a mean Attention Score of 4.6. This one is in the 15th percentile – i.e., 15% 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 230,682 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 35th percentile – i.e., 35% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 35 others from the same source and published within six weeks on either side of this one. This one is in the 48th percentile – i.e., 48% of its contemporaries scored the same or lower than it.