Epigenetic alterations involved in cancer stem cell reprogramming

Current hypotheses suggest that tumors originate from cells that carry out a process of “malignant reprogramming” driven by genetic and epigenetic alterations. Multiples studies reported the existence of stem-cell-like cells that acquire the ability to self-renew and are able to generate the bulk of more differentiated cells that form the tumor. This population of cancer cells, called cancer stem cells (CSC), is responsible for sustaining the tumor growth and, under determined conditions, can disseminate and migrate to give rise to secondary tumors or metastases to distant organs. Furthermore, CSCs have shown to be more resistant to anti-tumor treatments than the non-stem cancer cells, suggesting that surviving CSCs could be responsible for tumor relapse after therapy. These important properties have raised the interest in understanding the mechanisms that govern the generation and maintenance of this special population of cells, considered to lie behind the on/off switches of gene expression patterns. In this review, we summarize the most relevant epigenetic alterations, from DNA methylation and histone modifications to the recently discovered miRNAs that contribute to the regulation of cancer stem cell features in tumor progression, metastasis and response to chemotherapy.