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X Demographics
Mendeley readers
Attention Score in Context
| Title |
Dasatinib blocks transcriptional and promigratory responses to transforming growth factor-beta in pancreatic adenocarcinoma cells through inhibition of Smad signalling: implications for in vivo mode of action
|
|---|---|
| Published in |
Molecular Cancer, November 2015
|
| DOI | 10.1186/s12943-015-0468-0 |
| Pubmed ID | |
| Authors |
Tobias Bartscht, Benjamin Rosien, Dirk Rades, Roland Kaufmann, Harald Biersack, Hendrik Lehnert, Frank Gieseler, Hendrik Ungefroren |
| Abstract |
We have previously shown in pancreatic ductal adenocarcinoma (PDAC) cells that the SRC inhibitors PP2 and PP1 effectively inhibited TGF-β1-mediated cellular responses by blocking the kinase function of the TGF-β type I receptor ALK5 rather than SRC. Here, we investigated the ability of the clinically utilised SRC/ABL inhibitor dasatinib to mimic the PP2/PP1 effect. The effect of dasatinib on TGF-β1-dependent Smad2/3 phosphorylation, general transcriptional activity, gene expression, cell motility, and the generation of tumour stem cells was measured in Panc-1 and Colo-357 cells using immunoblotting, reporter gene assays, RT-PCR, impedance-based real-time measurement of cell migration, and colony formation assays, respectively. In both PDAC cell lines, dasatinib effectively blocked TGF-β1-induced Smad phosphorylation, activity of 3TPlux and pCAGA(12)-luc reporter genes, cell migration, and expression of individual TGF-β1 target genes associated with epithelial-mesenchymal transition and invasion. Moreover, dasatinib strongly interfered with the TGF-β1-induced generation of tumour stem cells as demonstrated by gene expression analysis and single cell colony formation. Dasatinib also inhibited the high constitutive migratory activity conferred on Panc-1 cells by ectopic expression of kinase-active ALK5. Our data suggest that the clinical efficiency of dasatinib may in part be due to cross-inhibition of tumour-promoting TGF-β signalling. Dasatinib may be useful as a dual TGF-β/SRC inhibitor in experimental and clinical therapeutics to prevent metastatic spread in late-stage PDAC and other tumours. |
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 % |
|---|---|---|
| Scientists | 1 | 100% |
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 % |
|---|---|---|
| Unknown | 24 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 5 | 21% |
| Student > Master | 4 | 17% |
| Researcher | 3 | 13% |
| Student > Bachelor | 2 | 8% |
| Student > Doctoral Student | 2 | 8% |
| Other | 4 | 17% |
| Unknown | 4 | 17% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 6 | 25% |
| Medicine and Dentistry | 4 | 17% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 13% |
| Biochemistry, Genetics and Molecular Biology | 2 | 8% |
| Engineering | 2 | 8% |
| Other | 2 | 8% |
| Unknown | 5 | 21% |
Attention Score in Context
This research output has an Altmetric Attention Score of 4. 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 13 July 2023.
All research outputs
#7,634,384
of 24,535,155 outputs
Outputs from Molecular Cancer
#576
of 1,840 outputs
Outputs of similar age
#113,094
of 396,512 outputs
Outputs of similar age from Molecular Cancer
#9
of 35 outputs
Altmetric has tracked 24,535,155 research outputs across all sources so far. This one has received more attention than most of these and is in the 68th percentile.
So far Altmetric has tracked 1,840 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.5. This one has gotten more attention than average, scoring higher than 67% 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 396,512 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 70% of its contemporaries.
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 has done well, scoring higher than 77% of its contemporaries.