The Wnt gatekeeper SFRP4 modulates EMT, cell migration and downstream Wnt signalling in serous ovarian cancer cells

Ford, Caroline E., Jary, Eve, Ma, Sean Si Qian, Nixdorf, Sheri, Heinzelmann-Schwarz, Viola A. and Ward, Robyn L. (2013) The Wnt gatekeeper SFRP4 modulates EMT, cell migration and downstream Wnt signalling in serous ovarian cancer cells. PLoS ONE, 8 1: . doi:10.1371/journal.pone.0054362


Author Ford, Caroline E.
Jary, Eve
Ma, Sean Si Qian
Nixdorf, Sheri
Heinzelmann-Schwarz, Viola A.
Ward, Robyn L.
Title The Wnt gatekeeper SFRP4 modulates EMT, cell migration and downstream Wnt signalling in serous ovarian cancer cells
Journal name PLoS ONE   Check publisher's open access policy
ISSN 1932-6203
Publication date 2013-01-11
Year available 2013
Sub-type Article (original research)
DOI 10.1371/journal.pone.0054362
Open Access Status DOI
Volume 8
Issue 1
Total pages 7
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Abstract Aberrant Wnt signalling is implicated in numerous human cancers, and understanding the effects of modulation of pathway members may lead to the development of novel therapeutics. Expression of secreted frizzled related protein 4 (SFRP4), an extracellular modulator of the Wnt signalling pathway, is progressively lost in more aggressive ovarian cancer phenotypes. Here we show that recombinant SFRP4 (rSFRP4) treatment of a serous ovarian cancer cell line results in inhibition of β-catenin dependent Wnt signalling as measured by TOP/FOP Wnt reporter assay and decreased transcription of Wnt target genes, Axin2, CyclinD1 and Myc. In addition, rSFRP4 treatment significantly increased the ability of ovarian cancer cells to adhere to collagen and fibronectin, and decreased their ability to migrate across an inflicted wound. We conclude that these changes in cell behaviour may be mediated via mesenchymal to epithelial transition (MET), as rSFRP4 treatment also resulted in increased expression of the epithelial marker E-cadherin, and reduced expression of Vimentin and Twist. Combined, these results indicate that modulation of a single upstream gatekeeper of Wnt signalling can have effects on downstream Wnt signalling and ovarian cancer cell behaviour, as mediated through epithelial to mesenchymal plasticity (EMP). This raises the possibility that SFRP4 may be used both diagnostically and therapeutically in epithelial ovarian cancer.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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