Multifaceted Roles of DNA Methylation in Neoplastic Transformation, from Tumor Suppressors to EMT and Metastasis
Among the major mechanisms involved in tumorigenesis, DNA methylation is an important epigenetic modification impacting both genomic stability and gene expression. Methylation of promoter-proximal CpG islands (CGIs) and transcriptional silencing of tumor suppressors represent the best characterized...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-08-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/11/8/922 |
| _version_ | 1797558732657262592 |
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| author | Laura Casalino Pasquale Verde |
| author_facet | Laura Casalino Pasquale Verde |
| author_sort | Laura Casalino |
| collection | DOAJ |
| description | Among the major mechanisms involved in tumorigenesis, DNA methylation is an important epigenetic modification impacting both genomic stability and gene expression. Methylation of promoter-proximal CpG islands (CGIs) and transcriptional silencing of tumor suppressors represent the best characterized epigenetic changes in neoplastic cells. The global cancer-associated effects of DNA hypomethylation influence chromatin architecture and reactivation of repetitive elements. Moreover, recent analyses of cancer cell methylomes highlight the role of the DNA hypomethylation of super-enhancer regions critically controlling the expression of key oncogenic players. We will first summarize some basic aspects of DNA methylation in tumorigenesis, along with the role of dysregulated DNA methyltransferases and TET (Ten-Eleven Translocation)-family methylcytosine dioxygenases. We will then examine the potential contribution of epimutations to causality and heritability of cancer. By reviewing some representative genes subjected to hypermethylation-mediated silencing, we will survey their oncosuppressor functions and roles as biomarkers in various types of cancer. Epithelial-to-mesenchymal transition (EMT) and the gain of stem-like properties are critically involved in cancer cell dissemination, metastasis, and therapeutic resistance. However, the driver vs passenger roles of epigenetic changes, such as DNA methylation in EMT, are still poorly understood. Therefore, we will focus our attention on several aspects of DNA methylation in control of EMT and metastasis suppressors, including both protein-coding and noncoding genes. |
| first_indexed | 2024-03-10T17:35:40Z |
| format | Article |
| id | doaj.art-89f6e5c2635a427793ade1db4a3f7b5c |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T17:35:40Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-89f6e5c2635a427793ade1db4a3f7b5c2023-11-20T09:51:52ZengMDPI AGGenes2073-44252020-08-0111892210.3390/genes11080922Multifaceted Roles of DNA Methylation in Neoplastic Transformation, from Tumor Suppressors to EMT and MetastasisLaura Casalino0Pasquale Verde1Institute of Genetics and Biophysics “Adriano Buzzati Traverso”, CNR, 80100 Naples, ItalyInstitute of Genetics and Biophysics “Adriano Buzzati Traverso”, CNR, 80100 Naples, ItalyAmong the major mechanisms involved in tumorigenesis, DNA methylation is an important epigenetic modification impacting both genomic stability and gene expression. Methylation of promoter-proximal CpG islands (CGIs) and transcriptional silencing of tumor suppressors represent the best characterized epigenetic changes in neoplastic cells. The global cancer-associated effects of DNA hypomethylation influence chromatin architecture and reactivation of repetitive elements. Moreover, recent analyses of cancer cell methylomes highlight the role of the DNA hypomethylation of super-enhancer regions critically controlling the expression of key oncogenic players. We will first summarize some basic aspects of DNA methylation in tumorigenesis, along with the role of dysregulated DNA methyltransferases and TET (Ten-Eleven Translocation)-family methylcytosine dioxygenases. We will then examine the potential contribution of epimutations to causality and heritability of cancer. By reviewing some representative genes subjected to hypermethylation-mediated silencing, we will survey their oncosuppressor functions and roles as biomarkers in various types of cancer. Epithelial-to-mesenchymal transition (EMT) and the gain of stem-like properties are critically involved in cancer cell dissemination, metastasis, and therapeutic resistance. However, the driver vs passenger roles of epigenetic changes, such as DNA methylation in EMT, are still poorly understood. Therefore, we will focus our attention on several aspects of DNA methylation in control of EMT and metastasis suppressors, including both protein-coding and noncoding genes.https://www.mdpi.com/2073-4425/11/8/922DNA methylationneoplastic transformationtumor suppressorsbiomarkersepithelial-to-mesenchymal transitionmetastasis |
| spellingShingle | Laura Casalino Pasquale Verde Multifaceted Roles of DNA Methylation in Neoplastic Transformation, from Tumor Suppressors to EMT and Metastasis Genes DNA methylation neoplastic transformation tumor suppressors biomarkers epithelial-to-mesenchymal transition metastasis |
| title | Multifaceted Roles of DNA Methylation in Neoplastic Transformation, from Tumor Suppressors to EMT and Metastasis |
| title_full | Multifaceted Roles of DNA Methylation in Neoplastic Transformation, from Tumor Suppressors to EMT and Metastasis |
| title_fullStr | Multifaceted Roles of DNA Methylation in Neoplastic Transformation, from Tumor Suppressors to EMT and Metastasis |
| title_full_unstemmed | Multifaceted Roles of DNA Methylation in Neoplastic Transformation, from Tumor Suppressors to EMT and Metastasis |
| title_short | Multifaceted Roles of DNA Methylation in Neoplastic Transformation, from Tumor Suppressors to EMT and Metastasis |
| title_sort | multifaceted roles of dna methylation in neoplastic transformation from tumor suppressors to emt and metastasis |
| topic | DNA methylation neoplastic transformation tumor suppressors biomarkers epithelial-to-mesenchymal transition metastasis |
| url | https://www.mdpi.com/2073-4425/11/8/922 |
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