| Title |
Tartrate-resistant acid phosphatase (TRAP/ACP5) promotes metastasis-related properties via TGFβ2/TβR and CD44 in MDA-MB-231 breast cancer cells
|
|---|---|
| Published in |
BMC Cancer, September 2017
|
| DOI | 10.1186/s12885-017-3616-7 |
| Pubmed ID | |
| Authors |
Anja Reithmeier, Elena Panizza, Michael Krumpel, Lukas M. Orre, Rui M. M. Branca, Janne Lehtiö, Barbro Ek-Rylander, Göran Andersson |
| Abstract |
Tartrate-resistant acid phosphatase (TRAP/ACP5), a metalloenzyme that is characteristic for its expression in activated osteoclasts and in macrophages, has recently gained considerable focus as a driver of metastasis and was associated with clinically relevant parameters of cancer progression and cancer aggressiveness. MDA-MB-231 breast cancer cells with different TRAP expression levels (overexpression and knockdown) were generated and characterized for protein expression and activity levels. Functional cell experiments, such as proliferation, migration and invasion assays were performed as well as global phosphoproteomic and proteomic analysis was conducted to connect molecular perturbations to the phenotypic changes. We identified an association between metastasis-related properties of TRAP-overexpressing MDA-MB-231 breast cancer cells and a TRAP-dependent regulation of Transforming growth factor (TGFβ) pathway proteins and Cluster of differentiation 44 (CD44). Overexpression of TRAP increased anchorage-independent and anchorage-dependent cell growth and proliferation, induced a more elongated cellular morphology and promoted cell migration and invasion. Migration was increased in the presence of the extracellular matrix (ECM) proteins osteopontin and fibronectin and the basement membrane proteins collagen IV and laminin I. TRAP-induced properties were reverted upon shRNA-mediated knockdown of TRAP or treatment with the small molecule TRAP inhibitor 5-PNA. Global phosphoproteomics and proteomics analyses identified possible substrates of TRAP phosphatase activity or signaling intermediates and outlined a TRAP-dependent regulation of proteins involved in cell adhesion and ECM organization. Upregulation of TGFβ isoform 2 (TGFβ2), TGFβ receptor type 1 (TβR1) and Mothers against decapentaplegic homolog 2 (SMAD2), as well as increased intracellular phosphorylation of CD44 were identified upon TRAP perturbation. Functional antibody-mediated blocking and chemical inhibition demonstrated that TRAP-dependent migration and proliferation is regulated via TGFβ2/TβR, whereas proliferation beyond basal levels is regulated through CD44. Altogether, TRAP promotes metastasis-related cell properties in MDA-MB-231 breast cancer cells via TGFβ2/TβR and CD44, thereby identifying a potential signaling mechanism associated to TRAP action in breast cancer cells. |
X Demographics
The data shown below were collected from the profiles of 5 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 2 | 40% |
| Sweden | 1 | 20% |
| United Kingdom | 1 | 20% |
| Unknown | 1 | 20% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 60% |
| Scientists | 2 | 40% |
Mendeley readers
The data shown below were compiled from readership statistics for 51 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 51 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 9 | 18% |
| Student > Ph. D. Student | 7 | 14% |
| Student > Bachelor | 7 | 14% |
| Researcher | 6 | 12% |
| Professor > Associate Professor | 3 | 6% |
| Other | 6 | 12% |
| Unknown | 13 | 25% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 14 | 27% |
| Agricultural and Biological Sciences | 7 | 14% |
| Medicine and Dentistry | 3 | 6% |
| Computer Science | 2 | 4% |
| Immunology and Microbiology | 2 | 4% |
| Other | 7 | 14% |
| Unknown | 16 | 31% |
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 2021.
All research outputs
#8,089,575
of 25,186,033 outputs
Outputs from BMC Cancer
#2,177
of 8,895 outputs
Outputs of similar age
#118,333
of 321,925 outputs
Outputs of similar age from BMC Cancer
#37
of 115 outputs
Altmetric has tracked 25,186,033 research outputs across all sources so far. This one has received more attention than most of these and is in the 67th percentile.
So far Altmetric has tracked 8,895 research outputs from this source. They receive a mean Attention Score of 4.6. This one has done well, scoring higher than 75% 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 321,925 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 62% of its contemporaries.
We're also able to compare this research output to 115 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 68% of its contemporaries.