The roles of ZEB1 in tumorigenic progression and epigenetic modifications

Highly expressed Zinc-finger E-box binding protein 1 (ZEB1) is significantly associated with the malignancy of various cancers. Signal transduction and activation of ZEB1 play important roles in cancer transformation and epithelial-mesenchymal transition (EMT). Emerging evidence suggests that ZEB1 drives the induction of EMT with activation of stem cell traits, immune evasion and epigenetic reprogramming. As an ideal target for EMT research, ZEB1 has been extensively studied for decades. However, the link between ZEB1 and epigenetic regulation of EMT has only recently been discovered. ZEB1 facilitates the epigenetic silencing of E-cadherin by recruiting multiple chromatin enzymes of E-cadherin promoter, such as histone deacetylases (HDACs), DNA methyltransferase (DNMT) and ubiquitin ligase. Destruction of the connection between ZEB1 and these chromatin-modifying enzymes may represent an efficient for treating cancer. In this review, we outlined the biological function of ZEB1 in tumorigenic progression and epigenetic modifications and elucidate its transcriptional network, which is a suitable potential target for the design of novel anticancer drugs.