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

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 p...

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Veröffentlicht in:PloS one 2013-01, Vol.8 (1), p.e54362-e54362
Hauptverfasser: Ford, Caroline E, Jary, Eve, Ma, Sean Si Qian, Nixdorf, Sheri, Heinzelmann-Schwarz, Viola A, Ward, Robyn L
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container_title PloS one
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Jary, Eve
Ma, Sean Si Qian
Nixdorf, Sheri
Heinzelmann-Schwarz, Viola A
Ward, Robyn L
description 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.
doi_str_mv 10.1371/journal.pone.0054362
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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. 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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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23326605</pmid><doi>10.1371/journal.pone.0054362</doi><tpages>e54362</tpages><oa>free_for_read</oa></addata></record>
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subjects Aberration
beta Catenin - genetics
beta Catenin - metabolism
Biology
Cancer
Cancer cells
Carcinoma, Ovarian Epithelial
Care and treatment
Cell cycle
Cell Line, Tumor
Cell migration
Cell Movement - genetics
Children & youth
Childrens health
Collagen
Downstream effects
Drug development
E-cadherin
Epithelial-Mesenchymal Transition
Female
Fibronectin
Fibronectins
Frizzled protein
Genes
Genetic Vectors
Humans
Intermediate filament proteins
Low density lipoprotein receptors
Medical prognosis
Medical research
Medicine
Mesenchyme
Metastasis
Modulation
Molecular Targeted Therapy
Myc protein
Neoplasms, Glandular and Epithelial - genetics
Neoplasms, Glandular and Epithelial - pathology
Ovarian cancer
Ovarian carcinoma
Ovarian Neoplasms - genetics
Ovarian Neoplasms - pathology
Penicillin
Prostate cancer
Proteins
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - metabolism
Recombinant Proteins - genetics
Recombinant Proteins - metabolism
Signal transduction
Signaling
Stem cells
Studies
Transcription
Transcription (Genetics)
Transfection
Tumors
Vimentin
Wnt protein
Wnt Signaling Pathway - genetics
Wounds
β-Catenin
title The Wnt gatekeeper SFRP4 modulates EMT, cell migration and downstream Wnt signalling in serous ovarian cancer cells
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