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The pseudokinase SgK223 promotes invasion of pancreatic ductal epithelial cells through JAK1/Stat3 signaling

Overview of attention for article published in Molecular Cancer, July 2015
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  • Above-average Attention Score compared to outputs of the same age (64th percentile)
  • Good Attention Score compared to outputs of the same age and source (79th percentile)

Mentioned by

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4 tweeters

Citations

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25 Dimensions

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22 Mendeley
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Title
The pseudokinase SgK223 promotes invasion of pancreatic ductal epithelial cells through JAK1/Stat3 signaling
Published in
Molecular Cancer, July 2015
DOI 10.1186/s12943-015-0412-3
Pubmed ID
Authors

Carole M. Tactacan, Yu Wei Phua, Ling Liu, Luxi Zhang, Emily S. Humphrey, Mark Cowley, Mark Pinese, Andrew V. Biankin, Roger J. Daly

Abstract

Characterization of molecular mechanisms underpinning development of pancreatic ductal adenocarcinoma (PDAC) may lead to the identification of novel therapeutic targets and biomarkers. SgK223, also known as Pragmin, is a pseudokinase and scaffolding protein closely related to SgK269/PEAK1. Both proteins are implicated in oncogenic tyrosine kinase signaling, but their mechanisms and function remain poorly characterized. Expression of SgK223 in PDAC and PDAC cell lines was characterized using gene expression microarrays, mass spectrometry (MS)-based phosphoproteomics and Western blotting. SgK223 was overexpressed in human pancreatic ductal epithelial (HPDE) cells via retroviral transduction, and knocked down in PDAC cells using siRNA. Cell proliferation was determined using a colorimetric cell viability assay, and cell migration and invasion using transwells. Expression of markers of epithelial-mesenchyme transition (EMT) was assayed by quantitative PCR. SgK223 and Stat3 signaling was interrogated by immunoprecipitation, Western blot and gene reporter assays. The functional role of specific kinases and Stat3 was determined using selective small molecule inhibitors. Elevated site-selective tyrosine phosphorylation of SgK223 was identified in subsets of PDAC cell lines, and increased expression of SgK223 detected in several PDAC cell lines compared to human pancreatic ductal epithelial (HPDE) cells and in PDACs compared to normal pancreas. Expression of SgK223 in HPDE cells at levels comparable to those in PDAC did not alter cell proliferation but led to a more elongated morphology, enhanced migration and invasion and induced gene expression changes characteristic of a partial EMT. While SgK223 overexpression did not affect activation of Erk or Akt, it led to increased Stat3 Tyr705 phosphorylation and Stat3 transcriptional activity, and SgK223 and Stat3 associated in vivo. SgK223-overexpressing cells exhibited increased JAK1 activation, and use of selective inhibitors determined that the increased Stat3 signaling driven by SgK223 was JAK-dependent. Pharmacological inhibition of Stat3 revealed that Stat3 activation was required for the enhanced motility and invasion of SgK223-overexpressing cells. Increased expression of SgK223 occurs in PDAC, and overexpression of SgK223 in pancreatic ductal epithelial cells promotes acquisition of a migratory and invasive phenotype through enhanced JAK1/Stat3 signaling. This represents the first association of SgK223 with a particular human cancer, and links SgK223 with a major signaling pathway strongly implicated in PDAC progression.

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 22 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 22 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 27%
Researcher 5 23%
Other 3 14%
Student > Doctoral Student 3 14%
Student > Postgraduate 2 9%
Other 1 5%
Unknown 2 9%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 10 45%
Agricultural and Biological Sciences 8 36%
Medicine and Dentistry 2 9%
Unknown 2 9%

Attention Score in Context

This research output has an Altmetric Attention Score of 3. 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 16 August 2015.
All research outputs
#5,744,615
of 11,254,718 outputs
Outputs from Molecular Cancer
#345
of 969 outputs
Outputs of similar age
#82,270
of 235,180 outputs
Outputs of similar age from Molecular Cancer
#9
of 44 outputs
Altmetric has tracked 11,254,718 research outputs across all sources so far. This one is in the 48th percentile – i.e., 48% of other outputs scored the same or lower than it.
So far Altmetric has tracked 969 research outputs from this source. They receive a mean Attention Score of 3.4. This one has gotten more attention than average, scoring higher than 64% 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 235,180 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 64% of its contemporaries.
We're also able to compare this research output to 44 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 79% of its contemporaries.