Figure 3. Metabolic-Epigenetic crosstalk in PDA.
epigenetics and metabolic pathways ultimately contribute to tumorigenesis. In murine PDA the metabolic reprograming due to activated KRASG12D expression promotes increase in H3 and H4 acetylation, via acetyl-CoA nuclear accumulation after AKT-dependent activation. Histone acetylation is usually associated with active gene transcription. CSCs expression have higher overall DNA methylation levels. SAM might contribute to DNA hypermethylation and increase in SAM availability enhances gene silencing through promotion of DNA methylation. DNMTs are overexpressed in several cancers and promote silencing of tumor suppressor genes in PDA. A DNA methylation inhibitor promoted reduced self-renewal marker expression. Additionally, several observations suggest links between environmental factors such as smoke sun and diet with an increased risks of cancer development [119].