Zinc finger E-box-binding homeobox 1 (ZEB1)

Zinc finger E-box-binding homeobox 1 (ZEB1) is a transcription factor characterized by two zinc finger clusters and a central homeodomain, enabling it to bind E-box sequences in DNA and regulate gene transcription[1][3][5][7]. ZEB1 can act as both transcriptional repressor and activator by recruiting various cofactors, significantly influencing cell fate decisions. ZEB1 is a pivotal regulator of epithelial-mesenchymal transition (EMT), facilitating tumor cell invasion, metastasis, chemoresistance, and the acquisition or maintenance of cancer stem cell phenotypes[1][3][4]. In normal physiology, ZEB1 is essential in embryonic development (e.g., neural crest and palate formation) but its specific adult roles are less well characterized[1]. Pathologically, overexpression or dysregulation of ZEB1 is strongly linked with aggressive cancers and poor clinical outcomes[1][4][5]. While there are no approved drugs directly targeting ZEB1, its role at the intersection of transcriptional regulation, tumor progression, immune evasion, and therapy resistance makes it a major research focus as a therapeutic target in oncology[1][3][4].

Other names

δEF1Nil-2-aTCF8ZEB-1

Inhibition or modulation of its transcriptional activity (therapeutic approaches under investigation in cancer focus on downregulation or antagonism of ZEB1 to overcome EMT-associated drug resistance)[1][4]