FH and cancer: In addition, ∆Np63α-arbitrated lymphoid-specific helicase (Lsh) upregulation77 can epigenetically suppress fumarate hydratase (FH), a Krebs cycle enzyme.81 This leads to the accumulation of fumarate, considered an oncometabolite, which then inhibits the inhibitors of hypoxia-inducible factor (HIF), the prolyl hydroxylases (PHDs).82 Consequently, amplified HIF can promote malignancy through the Warburg effect by providing cancer cells with building blocks (Fig. 3b).83