Zinc finger E-box-binding homeobox 2 (ZEB2) (ZEB2)

Zinc finger E-box-binding homeobox 2 (ZEB2) is a multi-zinc finger transcription factor that serves as a master regulator of the epithelial-mesenchymal transition (EMT) [UniProt: P57078]. It primarily functions as a transcriptional repressor by binding to E-box elements in the promoter of the CDH1 gene, leading to the downregulation of E-cadherin and the acquisition of invasive properties in cancer cells [PubMed: 28611511]. Beyond oncology, ZEB2 is essential for normal embryonic development, particularly in the formation of the neural crest, brain, and midline structures [NCBI Gene: 9839]. Germline mutations in ZEB2 result in Mowat-Wilson syndrome, characterized by intellectual disability, distinctive facial features, and Hirschsprung disease [OMIM: 605802]. While ZEB2 is a significant therapeutic target for preventing cancer metastasis, it is traditionally considered "undruggable" by small molecules, leading to research into RNA-based therapeutics and microRNA-200 family mimics to modulate its activity [PubMed: 30333564]. Its role in hematopoiesis and stem cell maintenance further complicates its profile as a drug target, requiring high specificity to avoid systemic toxicity [PubMed: 25239263]. Current drug discovery efforts also explore the inhibition of upstream activators or downstream effectors within the ZEB2 signaling network [PubMed: 31434666].

Other names

SMAD-interacting protein 1SIP1Zinc finger homeobox protein 1bZFHX1BSMADIP1

Transcriptional repression of E-cadherin (CDH1) and induction of mesenchymal gene expression to promote EMT.