Emma J. Wilkinson, Kelsie Raspin, Roslyn C. Malley, Shaun Donovan, Louise M. Nott, Adele F. Holloway, Joanne L. Dickinson
{"title":"WNT5A 是前列腺癌骨转移的假定外驱动因素。","authors":"Emma J. Wilkinson, Kelsie Raspin, Roslyn C. Malley, Shaun Donovan, Louise M. Nott, Adele F. Holloway, Joanne L. Dickinson","doi":"10.1002/cam4.70122","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Here, using Illumina Methylation EPIC array data of paired primary PrCa and metastatic bone samples, we identified <i>WNT5A</i> as a putative epi-driver of PrCa metastasis to the bone, which was further validated in vitro.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Significantly higher <i>WNT5A</i> 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 <i>WNT5A</i> gene expression.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Given the limited effective therapies available for metastatic cancer sufferers, particularly those whose disease has metastasised to the bone, <i>WNT5A</i> presents as a potential putative target for therapy.</p>\n </section>\n </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":null,"pages":null},"PeriodicalIF":2.9000,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70122","citationCount":"0","resultStr":"{\"title\":\"WNT5A is a putative epi-driver of prostate cancer metastasis to the bone\",\"authors\":\"Emma J. Wilkinson, Kelsie Raspin, Roslyn C. Malley, Shaun Donovan, Louise M. Nott, Adele F. Holloway, Joanne L. Dickinson\",\"doi\":\"10.1002/cam4.70122\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Here, using Illumina Methylation EPIC array data of paired primary PrCa and metastatic bone samples, we identified <i>WNT5A</i> as a putative epi-driver of PrCa metastasis to the bone, which was further validated in vitro.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Significantly higher <i>WNT5A</i> 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 <i>WNT5A</i> gene expression.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>Given the limited effective therapies available for metastatic cancer sufferers, particularly those whose disease has metastasised to the bone, <i>WNT5A</i> presents as a potential putative target for therapy.</p>\\n </section>\\n </div>\",\"PeriodicalId\":139,\"journal\":{\"name\":\"Cancer Medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2024-08-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70122\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/cam4.70122\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Medicine","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/cam4.70122","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
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.
期刊介绍:
Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas:
Clinical Cancer Research
Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations
Cancer Biology:
Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery.
Cancer Prevention:
Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach.
Bioinformatics:
Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers.
Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.