Epigenetic contributions to cancer metastasis.
The molecular basis of cancer encompasses both genetic and epigenetic alterations. These epigenetic changes primarily involve global DNA methylation changes in the form of widespread loss of methylation along with concurrent hypermethylation events in gene regulatory regions that can repress tissue-specific gene expression. Increasingly, the importance of these epigenetic changes to the metastatic process is being realized. Cells may acquire an epi-genotype that permits their dissemination from the primary tumour mass or the ability to survive and proliferate at a secondary tissue site. These epigenetic changes may be cancer-type specific, or in some cases may involve a common target gene providing a selective advantage to multiple metastatic cell types. In this review, I examine the growing volume of literature related to the epigenetic contributions to cancer metastasis. I discuss the functional importance of these epigenetic phenomena and how new epigenetic biomarkers may permit the identification of diagnostic signatures of metastasis and the development of new cancer therapies.
Rodenhiser
David I
DI
Departments of Biochemistry, Oncology and Paediatrics, University of Western Ontario, London, Ontario, Canada. drodenhi@uwo.ca
D019175:DNA Methylation; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D006801:Humans; D009362:Neoplasm Metastasis / Q000235:genetics*; D011401:Promoter Regions, Genetic