Methylation and Loss of Secreted Frizzled-Related Protein 3 Enhances Melanoma Cell Migration and Invasion

Ekstrom, Elin J., Sherwood, Victoria and Andersson, Tommy (2011) Methylation and Loss of Secreted Frizzled-Related Protein 3 Enhances Melanoma Cell Migration and Invasion. PLoS One, 6 (4). ISSN 1932-6203

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Abstract

Background: Wnt signaling is important in development and can also contribute to the initiation and progression of cancer. The Secreted Frizzled Related Proteins (SFRPs) constitute a family of Wnt modulators, crucial for controlling Wnt signaling. Here we investigate the expression and role of SFRP3 in melanoma. Methodology/Principal Findings: We show that SFRP3 mRNA is down-regulated in malignant melanoma tumors as compared to normal/benign tissue. Furthermore, we found that SFRP3 expression was lost in the malignant melanoma cell lines, A2058, HTB63 and A375, but not in the non-transformed melanocyte cell line, Hermes 3A. Methylated CpG rich areas were detected in the SFRP3 gene in melanoma cell lines and their SFRP3 expression could be restored using the demethylating agent, 5'aza-deoxycytidine. Addition of recombinant SFRP3 to melanoma cells had no effect on viable cell numbers, but decreased cell migration and invasion. Wnt5a signaling has been shown to increase the migration and invasion of malignant melanoma cells, and high expression of Wnt5a in melanoma tumors has been connected to a poor prognosis. We found that recombinant SFRP3 could inhibit Wnt5a signaling, and that it inhibited melanoma cell migration and invasion in a Wnt5a-dependent manner. Conclusion/Significance: We conclude that SFRP3 functions as a melanoma migration and invasion suppressor by interfering with Wnt5a signaling.

Item Type: Article
Additional Information: © 2011 Ekström et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Uncontrolled Keywords: genes,beta-catenin,epigenetic inactivation,wnt antagonist,transcription,growth,cancer,expression,pathway,inhibition
Faculty \ School: Faculty of Science > School of Pharmacy
Depositing User: Rachel Smith
Date Deposited: 07 Jun 2011 16:02
Last Modified: 21 Apr 2020 16:37
URI: https://ueaeprints.uea.ac.uk/id/eprint/31978
DOI: 10.1371/journal.pone.0018674

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