Epigenetic regulation of the Hedgehog and Wnt pathways in cancer

The Hedgehog (Hh) and wingless-Int1 (Wnt) pathways are important for tissue patterning in the developing embryo. In adult tissue, both pathways are typically dormant but are activated under certain conditions such as tissue damage. Aberrant activation of these pathways by mutations in key pathway regulators contributes to the genesis and progression of several cancer types. In addition, the impact of epigenetic regulation of the Hh and Wnt pathways on cancer is becoming increasingly clear. In this review, current knowledge on the epigenetic control of Hh and Wnt and the impact on tumor formation will be discussed. First, the role of epigenetic control on ligand production will be discussed, followed by the epigenetic regulation of the extra– and intracellular pathway members. Furthermore, the epigenetic control of pathway target genes will be highlighted. Lastly, an overview of current therapeutic strategies to target aberrant epigenetic control of the Hh and Wnt pathways is provided.