Zinc finger E-box-binding homeobox 1 (ZEB1) and Zinc finger E-box-binding homeobox 2 (ZEB2) (ZEB1/ZEB2)

Zinc finger E-box-binding homeobox 1 and 2 (ZEB1 and ZEB2) are key transcription factors that play a pivotal role in the epithelial-mesenchymal transition (EMT), a process essential for embryonic development and wound healing (UniProt P37275, O60315). In oncology, ZEB1 and ZEB2 are frequently upregulated, acting as potent repressors of E-cadherin, which promotes tumor cell invasion, metastasis, and the acquisition of cancer stem cell properties (PubMed: 28611478). Beyond cancer, mutations in ZEB2 are the primary cause of Mowat-Wilson syndrome, a multi-system developmental disorder characterized by intellectual disability and distinct facial features (NIH GeneReviews). While direct pharmacological inhibition of these transcription factors remains a significant challenge, therapeutic strategies focus on modulating upstream signaling pathways like TGF-beta or using microRNA-based approaches, such as miR-200 mimics, to silence their expression (PubMed: 25108232). Targeting the ZEB family is considered a promising strategy to reverse chemoresistance and inhibit the metastatic spread of aggressive solid tumors.

Other names

Transcription factor 8 (TCF8)Zinc finger homeobox protein 1a (ZFHX1A)Delta crystallin enhancer binding factor 1 (DELTAEF1)Smad-interacting protein 1 (SIP1)Zinc finger homeobox protein 1b (ZFHX1B)AREB6BZPNIL2AZFHEPSMADIP1

ZEB1 and ZEB2 primarily function as transcriptional repressors by binding to E-box motifs (5'-CANNTG-3') in the promoters of target genes, such as CDH1 (E-cadherin), and recruiting co-repressor complexes including C-terminal binding protein (CtBP) and histone deacetylases (HDACs) (PubMed: 21706045). They can also act as transcriptional activators in specific contexts, particularly when interacting with SMAD proteins in the TGF-beta signaling pathway.