ZEB1 and osteosarcoma: ZEB1 interacts with SMAD protein or with p300-P/CAF and activates TGF-β responsive genes to promote the EMT.117,118 Among ZEB1-activated genes, CDH2 (N-cadherin), a mesenchymal cadherin, is important in cancer progression (Figure 3b) given that altered expression of ZEB1 is observed in several human cancers, including pancreatic cancer, lung cancer, liver cancer, osteosarcoma, breast cancer, and colon cancer.109,119–122 Furthermore, the overexpression of ZEB1 in several cancer lines induces the EMT and promotes cell invasion.123,124