Epigenetic Mechanisms Involved in Cancer Stem Cell Profiles

Abstract

Epigenetic changes have been linked to abnormal transcriptional regulations which may result in carcinogenesis. Indeed, alterations in DNA methylation, histone modifications, polycomb, miRNAs, and chromatin remodeling complex function are mechanisms that directly contribute to tumorigenesis. Interestingly, the epigenetic origins of some of the aberrant signals that operate in tumor progression facilitate their reversion by specific inhibitors. In consequence, targeting the stemness-like properties of this special population of cancer cells with agents that modify their epigenetic landscape can contribute to the sensitization of CSCs to chemotherapy, impeding tumor relapse. For all these reasons, it is a rapidly emerging field in oncology and might represent a promising strategy for cancer therapy in the future. From all of epigenetic phenomena, DNA methylation is the most extensively studied epigenetic mechanism. Aberrant patterns of DNA methylation (hypomethylation or hypermethylation) are considered significant features in the diagnosis and/or prognosis of cancers. There is increasing evidence that DNA hypermethylation in gene promoter regions and its association with polycomb complex proteins may promote carcinogenesis by blocking certain normal stem cell patterns from fully differentiating, and consequently perpetuating self-renewal of these stem cells.