FIGURE 1.

Illustration of autocrine and paracrine signaling pathways in colorectal cancer. Diagram shows how numerous oncogenic signaling pathways, including Wnt, PDGF, c-MET, and KRAS, converge to effect epigenomes that facilitate pro-neoplastic (“dedifferentiation”) gene transcription. Possible points of epigenetic interventions, potentially reversing dedifferentiating epigenomes, are shown. For example activation of epithelial-to-mesenchymal transcription factors (e.g., Twist) leads to whole-genome chromatin remodeling and phenotypic plasticity, which can be inhibited or reversed.