DNA methylation and demethylation as targets for anticancer therapy.
Cancer growth and metastasis require the coordinate change in gene expression of different sets of genes. While genetic alterations can account for some of these changes, it is becoming evident that many of the changes in gene expression observed are caused by epigenetic modifications. The epigenome consists of the chromatin and its modifications, the "histone code" as well as the pattern of distribution of covalent modifications of cytosines residing in the dinucleotide sequence CG by methylation. Although hypermethylation of tumor suppressor genes has attracted a significant amount of attention and inhibitors of DNA methylation were shown to activate methylated tumor suppressor genes and inhibit tumor growth, demethylation of critical genes plays a critical role in cancer as well. This review discusses the emerging role of demethylation in activation of pro-metastatic genes and the potential therapeutic implications of the demethylation machinery in metastasis.
Szyf
M
M
Department of Pharmacology and Therapeutics, McGill University, Montreal PQ H3G 1Y6, Canada. moshe.szyf@mcgill.ca
D000818:Animals; D002843:Chromatin / Q000235:genetics / Q000648:ultrastructure; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D015254:DNA Modification Methylases / Q000378:metabolism; D004260:DNA Repair; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D044127:Epigenesis, Genetic / Q000235:genetics*; D006801:Humans; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000235:genetics*; D009369:Neoplasms / Q000188:drug therapy / Q000503:physiopathology; D020319:Oligodeoxyribonucleotides, Antisense / Q000627:therapeutic use
D002843:Chromatin; D004791:Enzyme Inhibitors; D020319:Oligodeoxyribonucleotides, Antisense; D015254:DNA Modification Methylases; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases