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Invasion of ovarian cancer cells is induced byPITX2-mediated activation of TGF-β and Activin-A

Overview of attention for article published in Molecular Cancer, August 2015
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Title
Invasion of ovarian cancer cells is induced byPITX2-mediated activation of TGF-β and Activin-A
Published in
Molecular Cancer, August 2015
DOI 10.1186/s12943-015-0433-y
Pubmed ID
Authors

Moitri Basu, Rahul Bhattacharya, Upasana Ray, Satinath Mukhopadhyay, Uttara Chatterjee, Sib Sankar Roy

Abstract

Most ovarian cancers are highly invasive in nature and the high burden of metastatic disease make them a leading cause of mortality among all gynaecological malignancies. The homeodomain transcription factor, PITX2 is associated with cancer in different tissues. Our previous studies demonstrated increased PITX2 expression in human ovarian tumours. Growing evidence linking activation of TGF-β pathway by homeodomain proteins prompted us to look for the possible involvement of this signalling pathway in PITX2-mediated progression of ovarian cancer. The status of TGF-β signalling in human ovarian tissues was assessed by immunohistochemistry. The expression level of TGFB/INHBA and other invasion-associated genes was measured by quantitative-PCR (Q-PCR) and Western Blot after transfection/treatments with clones/reagents in normal/cancer cells. The physiological effect of PITX2 on invasion/motility was checked by matrigel invasion and wound healing assay. The PITX2- and activin-induced epithelial-mesenchymal transition (EMT) was evaluated by Q-PCR of respective markers and confocal/phase-contrast imaging of cells. Human ovarian tumours showed enhanced TGF-β signalling. Our study uncovers the PITX2-induced expression of TGFB1/2/3 as well as INHBA genes (p < 0.01) followed by SMAD2/3-dependent TGF-β signalling pathway. PITX2-induced TGF-β pathway regulated the expression of invasion-associated genes, SNAI1, CDH1 and MMP9 (p < 0.01) that accounted for enhanced motility/invasion of ovarian cancers. Snail and MMP9 acted as important mediators of PITX2-induced invasiveness of ovarian cancer cells. PITX2 over-expression resulted in loss of epithelial markers (p < 0.01) and gain of mesenchymal markers (p < 0.01) that contributed significantly to ovarian oncogenesis. PITX2-induced INHBA expression (p < 0.01) contributed to EMT in both normal and ovarian cancer cells. Overall, our findings suggest a significant contributory role of PITX2 in promoting invasive behaviour of ovarian cancer cells through up-regulation of TGFB/INHBA. We have also identified the previously unknown involvement of activin-A in promoting EMT. Our work provides novel mechanistic insights into the invasive behavior of ovarian cancer cells. The extension of this study have the potential for therapeutic applications in future.

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The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 53 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Malaysia 1 2%
Unknown 52 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 14 26%
Student > Master 6 11%
Student > Doctoral Student 4 8%
Researcher 4 8%
Other 4 8%
Other 10 19%
Unknown 11 21%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 12 23%
Agricultural and Biological Sciences 9 17%
Medicine and Dentistry 8 15%
Immunology and Microbiology 3 6%
Computer Science 2 4%
Other 5 9%
Unknown 14 26%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 18 May 2016.
All research outputs
#14,235,639
of 22,824,164 outputs
Outputs from Molecular Cancer
#902
of 1,721 outputs
Outputs of similar age
#138,167
of 266,654 outputs
Outputs of similar age from Molecular Cancer
#23
of 46 outputs
Altmetric has tracked 22,824,164 research outputs across all sources so far. This one is in the 35th percentile – i.e., 35% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,721 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.7. This one is in the 43rd percentile – i.e., 43% 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 266,654 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 45th percentile – i.e., 45% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 46 others from the same source and published within six weeks on either side of this one. This one is in the 43rd percentile – i.e., 43% of its contemporaries scored the same or lower than it.