دورية أكاديمية

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

التفاصيل البيبلوغرافية
العنوان: The WNT gatekeeper SFRP4 modulates EMT, cell migration and downstream WNT signalling in serous ovarian cancer cells
المؤلفون: Ford, CE, Jary, E, Ma, SSQ, Nixdorf, S, Heinzelmann-Schwarz, VA, Ward, RL
المساهمون: Samant, Rajeev
المصدر: urn:ISSN:1932-6203 ; PLoS ONE, 8, 1, e54362
بيانات النشر: Public Library Science
سنة النشر: 2013
المجموعة: UNSW Sydney (The University of New South Wales): UNSWorks
مصطلحات موضوعية: Cancer, Rare Diseases, Ovarian Cancer, 5.1 Pharmaceuticals, 1.1 Normal biological development and functioning, 1 Underpinning research, 2.1 Biological and endogenous factors, 2 Aetiology, 5 Development of treatments and therapeutic interventions, Carcinoma, Ovarian Epithelial, Cell Line, Tumor, Cell Movement, Epithelial-Mesenchymal Transition, Female, Genetic Vectors, Humans, Molecular Targeted Therapy, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Proto-Oncogene Proteins, Recombinant Proteins, Transfection, Wnt Signaling Pathway, beta Catenin, anzsrc-for: 111201 Cancer Cell Biology
الوصف: 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 bcatenin 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.
نوع الوثيقة: article in journal/newspaper
اللغة: unknown
العلاقة: http://hdl.handle.net/1959.4/unsworks_53343Test; https://doi.org/10.1371/journal.pone.0054362Test
DOI: 10.1371/journal.pone.0054362
الإتاحة: https://doi.org/10.1371/journal.pone.0054362Test
http://hdl.handle.net/1959.4/unsworks_53343Test
حقوق: open access ; https://purl.org/coar/access_right/c_abf2Test ; CC BY ; https://creativecommons.org/licenses/by/4.0Test/
رقم الانضمام: edsbas.E3FE6565
قاعدة البيانات: BASE