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NFAT5-mediated expression of S100A4 contributes to proliferation and migration of renal carcinoma cells

Overview of attention for article published in Frontiers in Physiology, January 2014
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Title
NFAT5-mediated expression of S100A4 contributes to proliferation and migration of renal carcinoma cells
Published in
Frontiers in Physiology, January 2014
DOI 10.3389/fphys.2014.00293
Pubmed ID
Authors

Christoph Küper, Franz-Xaver Beck, Wolfgang Neuhofer

Abstract

The osmosensitive transcription factor nuclear factor of activated T-cells (NFAT) 5, also known as tonicity enhancer binding protein (TonEBP), has been associated with the development of a variety of tumor entities, among them breast cancer, colon carcinoma, and melanoma. The aim of the present study was to determine whether NFAT5 is also involved in the development of renal cell carcinoma (RCC). The most common type of RCC, the clear cell RCC, originates from the proximal convoluted tubule. We tested our hypothesis in the clear cell RCC cell line CaKi-1 and the non-cancerous proximal tubule cell line HK-2, as control. Basal expression of NFAT5 and NFAT5 activity in CaKi-1 cells was several times higher than in HK-2 cells. Osmotic stress induced an increased NFAT5 activity in both CaKi-1 and HK-2 cells, again with significantly higher activities in CaKi-1 cells. Analysis of NFAT5-regulating signaling pathways in CaKi-1 cells revealed that inhibition of the MAP kinases p38, c-Jun-terminal kinase (JNK) and extracellular regulated kinase (ERK) and of the focal adhesion kinase (FAK) partially blunted NFAT5 activity. FAK and ERK were both constitutively active, even under isotonic conditions, which may contribute to the high basal expression and activity of NFAT5 in CaKi-1 cells. In contrast, the MAP kinases p38 and JNK were inactive under isotonic conditions and became activated under osmotic stress conditions, indicating that p38 and JNK mediate upregulation of NFAT5 activity under these conditions. siRNA-mediated knockdown of NFAT5 in CaKi-1 cells reduced the expression of S100A4, a member of the S100 family of proteins, which promotes metastasis. Knockdown of NFAT5 was accompanied by a significant decrease in proliferation and migration activity. Taken together, our results indicate that NFAT5 induces S100A4 expression in CaKi-1 cells, thereby playing an important role in RCC proliferation and migration.

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Mendeley readers

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 %
Unknown 27 100%

Demographic breakdown

Readers by professional status Count As %
Student > Doctoral Student 6 22%
Student > Master 5 19%
Researcher 4 15%
Professor > Associate Professor 3 11%
Student > Ph. D. Student 2 7%
Other 4 15%
Unknown 3 11%
Readers by discipline Count As %
Agricultural and Biological Sciences 8 30%
Biochemistry, Genetics and Molecular Biology 8 30%
Medicine and Dentistry 5 19%
Chemical Engineering 1 4%
Neuroscience 1 4%
Other 0 0%
Unknown 4 15%
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 08 August 2014.
All research outputs
#20,233,547
of 22,759,618 outputs
Outputs from Frontiers in Physiology
#9,330
of 13,560 outputs
Outputs of similar age
#264,815
of 305,282 outputs
Outputs of similar age from Frontiers in Physiology
#73
of 106 outputs
Altmetric has tracked 22,759,618 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 13,560 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.5. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 106 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.