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Regulation of pancreatic stellate cell activation by Notch3

Overview of attention for article published in BMC Cancer, January 2018
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Title
Regulation of pancreatic stellate cell activation by Notch3
Published in
BMC Cancer, January 2018
DOI 10.1186/s12885-017-3957-2
Pubmed ID
Authors

Haiyan Song, Yuxiang Zhang

Abstract

Activated pancreatic stellate cells (PaSCs) are the key cellular source of cancer-associated fibroblasts in the pancreatic stroma of patients with pancreatic ductal adenocarcinoma (PDAC), however, the activation mechanism of PaSCs is not yet known. The Notch signaling pathway, components of which are expressed in stromal cells, is involved in the fibrosis of several organs, including the lung and liver. In the current study, we investigated whether Notch signal transduction is involved in PaSC activation in PDAC. The expression of Notch signaling pathway components in human PDAC was examined via immunohistochemical staining and assessed in mouse PaSCs using RT-qPCR and western blotting. Notch3 expression in both PDAC stromal cells and activated mouse PaSCs was evaluated using immunofluorescence, RT-qPCR and western blotting. The impact of siRNA-mediated Notch3 knockdown on PaSC activation was detected with RT-qPCR and western blotting, and the impact on PaSC proliferation and migration was detected using CCK-8 assays and scratch experiments. The effect of conditioned medium from PaSCs activated with Notch3 siRNA on pancreatic cancer (LTPA) cells was also detected with CCK-8 assays and scratch experiments. The data were analyzed for statistical significance using Student's t-test. Notch3 was overexpressed in both human PDAC stromal cells and activated mouse PaSCs, and Notch3 knockdown with Notch3 siRNA decreased the proliferation and migration of mouse PaSCs. The levels of markers related to PaSC activation, such as α-smooth muscle actin (α-SMA), collagen I and fibronectin, decreased in response to Notch3 knockdown, indicating that Notch3 plays an important role in PaSC activation. Furthermore, we confirmed that inhibition of PaSC activation via Notch3 siRNA reduced the proliferation and migration of PaSC-induced mouse pancreatic cancer (LTPA) cells. Notch3 inhibition in PaSCs can inhibit the activation, proliferation and migration of PaSCs and reduce the PaSC-induced pro-tumorigenic effect. Therefore, Notch3 silencing in PaSCs is a potential novel therapeutic option for patients with PDAC.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 39 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 39 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 7 18%
Researcher 6 15%
Student > Ph. D. Student 5 13%
Student > Master 4 10%
Lecturer 2 5%
Other 5 13%
Unknown 10 26%
Readers by discipline Count As %
Medicine and Dentistry 9 23%
Biochemistry, Genetics and Molecular Biology 8 21%
Agricultural and Biological Sciences 4 10%
Nursing and Health Professions 1 3%
Pharmacology, Toxicology and Pharmaceutical Science 1 3%
Other 4 10%
Unknown 12 31%
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 20 January 2018.
All research outputs
#18,583,054
of 23,016,919 outputs
Outputs from BMC Cancer
#5,462
of 8,359 outputs
Outputs of similar age
#330,383
of 441,878 outputs
Outputs of similar age from BMC Cancer
#141
of 203 outputs
Altmetric has tracked 23,016,919 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 8,359 research outputs from this source. They receive a mean Attention Score of 4.3. This one is in the 21st percentile – i.e., 21% 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 441,878 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 14th percentile – i.e., 14% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 203 others from the same source and published within six weeks on either side of this one. This one is in the 19th percentile – i.e., 19% of its contemporaries scored the same or lower than it.