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.
Source: The Wnt Gatekeeper SFRP4
Modulates EMT, Cell Migration and Downstream Wnt Signalling in Serous Ovarian
Cancer Cells. Ford CE (caroline.ford@unsw.edu.au), Jary E, Ma SS, Nixdorf
S, Heinzelmann-Schwarz VA, Ward RL. PLoS One. 2013;8(1):e54362.
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