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WNT5A 是前列腺癌骨转移的潜在上皮驱动因子。

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

机构信息

Tasmanian School of Medicine, University of Tasmania, Hobart, Tasmania, Australia.

Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.

出版信息

Cancer Med. 2024 Aug;13(16):e70122. doi: 10.1002/cam4.70122.

DOI:10.1002/cam4.70122
PMID:39164966
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11335815/
Abstract

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.

摘要

背景

目前的诊断工具无法区分低级别惰性前列腺癌（PrCa）与具有转移和/或致命倾向的前列腺癌。最近的证据表明，转录组的重编程可能驱动转移表型，并且这种重编程至少部分受到癌细胞 DNA 的表观遗传变化的控制，包括甲基化。这些变化被称为“表观遗传驱动因素”，以前与癌细胞存活有关。

方法

在这里，我们使用配对的原发性 PrCa 和转移性骨样本的 Illumina Methylation EPIC 阵列数据，鉴定出 WNT5A 是前列腺癌转移到骨骼的潜在表观遗传驱动因素，并在体外进一步验证。

结果

与转移性骨样本和 PC-3 细胞相比，原发性 PrCa 样本和 22Rv1 细胞中观察到 WNT5A 甲基化水平显著升高。这种更高的甲基化与 WNT5A 基因表达水平显著降低有关。

结论

鉴于转移性癌症患者，特别是那些已经转移到骨骼的患者，可用的有效治疗方法有限，WNT5A 作为一种潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86d7/11335815/6ea00502ca71/CAM4-13-e70122-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86d7/11335815/0eeb85c3706a/CAM4-13-e70122-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86d7/11335815/9a56d52d805c/CAM4-13-e70122-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86d7/11335815/66591cba99dc/CAM4-13-e70122-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86d7/11335815/10d0850451d6/CAM4-13-e70122-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86d7/11335815/6ea00502ca71/CAM4-13-e70122-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86d7/11335815/0eeb85c3706a/CAM4-13-e70122-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86d7/11335815/9a56d52d805c/CAM4-13-e70122-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86d7/11335815/66591cba99dc/CAM4-13-e70122-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86d7/11335815/10d0850451d6/CAM4-13-e70122-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86d7/11335815/6ea00502ca71/CAM4-13-e70122-g003.jpg

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Cells. 2023 Apr 8;12(8):1110. doi: 10.3390/cells12081110.
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Prostate Cancer Incidence and Mortality: Global Status and Temporal Trends in 89 Countries From 2000 to 2019.前列腺癌发病率和死亡率：2000 年至 2019 年 89 个国家的全球状况和时间趋势。
Front Public Health. 2022 Feb 16;10:811044. doi: 10.3389/fpubh.2022.811044. eCollection 2022.
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Elife. 2021 Oct 27;10:e65759. doi: 10.7554/eLife.65759.
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