Figure 1. Modulation of Twist1 expression by upstream regulators at both gene and protein levels.

Manifold extracellular insults (such as TNF-α, RTK ligands, WNT, TGF-β, Jagged1, EGF signaling and hypoxia) are transduced into the cell via trans-membrane receptors (TNFR, RTK, FZD, TGF-β, Notch and EGFR) and intracellular mediators in the cytosol (MAPK, AKT) and nucleus (NF-κB, MSX2, β-catenin, FBLN5, Smad, HMGA2, STAT3 and HIF-1α), thus regulating Twist1 expression at the gene level and Twist1 stability at the protein level, respectively. P, phosphrylation; Ub, Ubiquitination; RTK, receptor tyrosine kinases; EGF, epidermal growth factors; FZD, frizzed; GSK-3β, glycogen synthase kinase 3β; TCF, transcription factor; JAK2, janus kinase 2.