Received November 17, 2004
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.
KEY WORDS: DNA methylation, DNA demethylation, DNA methyltransferase (DNMT), DNA demethylase, MeCP2, MBD2, histone acetylation, epigenetics, epigenome, histone deacetylase (HDAC), TSA, HDAC inhibitors, metastasis