The non-canonical Wnt ligand, Wnt5a, is upregulated and associated with epithelial to mesenchymal transition in epithelial ovarian cancer

Ford, C. E., Punnia-Moorthy, G., Henry, C. E., Llamosas, E., Nixdorf, S., Olivier, J., Caduff, R., Ward, R. L. and Heinzelmann-Schwarz, V. (2014) The non-canonical Wnt ligand, Wnt5a, is upregulated and associated with epithelial to mesenchymal transition in epithelial ovarian cancer. Gynecologic Oncology, 134 2: 338-345. doi:10.1016/j.ygyno.2014.06.004


Author Ford, C. E.
Punnia-Moorthy, G.
Henry, C. E.
Llamosas, E.
Nixdorf, S.
Olivier, J.
Caduff, R.
Ward, R. L.
Heinzelmann-Schwarz, V.
Title The non-canonical Wnt ligand, Wnt5a, is upregulated and associated with epithelial to mesenchymal transition in epithelial ovarian cancer
Journal name Gynecologic Oncology   Check publisher's open access policy
ISSN 1095-6859
0090-8258
Publication date 2014-08
Year available 2014
Sub-type Article (original research)
DOI 10.1016/j.ygyno.2014.06.004
Open Access Status
Volume 134
Issue 2
Start page 338
End page 345
Total pages 8
Place of publication Maryland Heights MO, United States
Publisher Academic Press
Collection year 2015
Language eng
Formatted abstract
Objective

Aberrant Wnt signalling has previously been associated with gynaecological cancers, and the aim of this study was to investigate the expression of Wnt5a in epithelial ovarian cancer, and clarify its role in activating or inhibiting β-catenin dependent and independent Wnt signalling pathways.

Method

Wnt5a expression was investigated in a large cohort of epithelial ovarian cancer patient samples using immunohistochemistry and correlated with clinicopathological variables. Wnt5a function was investigated in vitro in ovarian cell lines.

Results

Wnt5a expression was found to be upregulated in all major subtypes (serous, endometrioid, clear cell and mucinous) of epithelial ovarian cancer compared to borderline tumours and benign controls. Treatment of ovarian surface epithelial cells with recombinant Wnt5a decreased cell adhesion and was associated with increased epithelial to mesenchymal transition (EMT). In addition, downstream targets of β-catenin dependent Wnt signalling were inhibited, and β-catenin independent targets increased following Wnt5a upregulation. Knockdown of Wnt5a in ovarian cancer cells was associated with a mesenchymal to epithelial transition (MET), but had no significant effect on cell migration or proliferation.

Conclusion

This study adds to the increasing evidence that Wnt signalling may play an important role in ovarian cancer development. Utilising an unparalleled large cohort of 623 patients, Wnt5a protein expression was shown to be significantly higher in ovarian cancer patients when compared to benign and borderline ovarian tumours and healthy control patients. In addition, we have utilised in vitro models to show for the first time in ovarian cancer that Wnt5a driven non-canonical pathways can alter epithelial to mesenchymal transition (EMT).
Keyword Wnt5a
Wnt signalling
Epithelial ovarian cancer
Metastasis
β-Catenin
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
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Created: Thu, 12 Feb 2015, 11:22:20 EST by Ms Kate Rowe on behalf of Office of Deputy Vice-Chancellor (Research)