WNT5A is a putative epi-driver of prostate cancer metastasis to the bone

Background: Current diagnostic tools are unable to distinguish low-grade indolent prostate cancer (PrCa) from that with a propensity to become metastatic and/or lethal. Recent evidence suggests that reprogramming of the transcriptome may drive the metastatic phenotype, and that this reprogramming is controlled, at least in part, by epigenetic changes to the DNA of cancer cells, including methylation. These changes, referred to as 'epigenetic drivers,' have previously been associated with cancer cell survival. Methods: Here, using Illumina Methylation EPIC array data of paired primary PrCa and metastatic bone samples, we identified WNT5A as a putative epi-driver of PrCa metastasis to the bone, which was further validated in vitro. Results: Significantly higher WNT5A methylation was observed in primary PrCa samples and 22Rv1 cells compared to metastatic bone samples and PC-3 cells. This higher methylation was associated with significantly lower WNT5A gene expression. Conclusion: Given the limited effective therapies available for metastatic cancer sufferers, particularly those whose disease has metastasised to the bone, WNT5A presents as a potential putative target for therapy.