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Signaling Pathways title  Epigenetic regulation

Epigenetic corresponds to the modifications of gene expression which do not arise from modifications of the DNA sequence. The most important events are: DNA methylation at CpG islets and post-translational modification of histones (1).

Signaling Pathways title  Normal conditions

In normal cells, these modifications allow to modulate gene expression, and numerous factors are involved in these mechanisms (DNA methyltransferase, histone deacetylase and histone acetyltransferase, sirtuin, aurora kinase,...) (2,3). All these factors interact together to modulate gene expression, which notably lead to cell differenciation of totipotent cell (3).

Epigenetic_regulation

 
Epigenetic control of adult stem cell function (4)
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Signaling Pathways title  Tumoral conditions

In cancer, tumor cells modulate epigenetic factors to their advantage. These mechanisms lead to transcription activation of genes involved in signaling pathways, ordinary inactive (migration, invasion, cell proliferation, ...) (5). These activations are due to global DNA hypomethylation with a localised hypermethylation (tumor suppressor genes and cell cycle checkpoints). Histones are also modified in order to let the chromatin more accessible (5).
Epigenetic events are strongly involved in the cell carcinogenesis and cell invasion in new tissues by metastasis process (6)
(1) Kinnaird A et al. Metabolic control of epigenetics in cancer. Nature (2016) 16: 694-707. 
(2) Chen QW et al. Epigenetic regulation and cancer (Review). Oncology reports (2014) 31: 523-532. 
(3) Cohen I et al. Histone Modifiers in Cancer: Friends or Foes? Genes & Cancer (2011) 2(6): 631-647. 
(4) Avgustinova A, Benitah SA. Epigenetic control of adult stem cell function. Nat Rev Mol Cell Biol. (2016) 17: 194-200. 
(5) Sharma S et al. Epigenetics in cancer. Carcinogenesis (2010) 31(1): 27-36. 
(6) Wu YS et al. Epigenetics in Metastatic Breast Cancer: Its Regulation and Implications in Diagnosis, Prognosis and Therapeutics. Curr Cancer Drug Targets. (2018).
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