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

Zinc finger E-box-binding homeobox 1 (ZEB1) is a crucial transcription factor that serves as a master regulator of the epithelial-mesenchymal transition (EMT), a process where epithelial cells lose their polarity and adhesion to become invasive mesenchymal cells (UniProt, 2024). It functions primarily by binding to E-box sequences in the promoters of target genes, most notably repressing the expression of E-cadherin (CDH1) to promote cell mobility and survival (PubMed, 2021). Beyond EMT, ZEB1 is involved in maintaining cancer cell stemness, regulating the DNA damage response, and conferring resistance to various therapeutic modalities, including chemotherapy and immunotherapy (Nature Reviews Cancer, 2013). In clinical oncology, high ZEB1 expression is frequently correlated with advanced tumor stage, metastasis, and poor patient prognosis across multiple malignancies such as breast, lung, and pancreatic cancers (PubMed, 2019). Although transcription factors like ZEB1 have historically been challenging to target directly with small molecules, current therapeutic strategies focus on modulating its activity through upstream signaling inhibitors, epigenetic modifiers like HDAC inhibitors, or microRNA-based approaches (Cancer Research, 2017). Furthermore, ZEB1 plays a role in non-malignant conditions, such as corneal dystrophies, where mutations in the ZEB1 gene lead to endothelial cell dysfunction (NCBI Gene, 2024).

Other names

Transcription factor 8TCF8AREB6BZPDELTAEF1NIL2AZFHEPZFHX1A

ZEB1 acts as a transcriptional repressor by binding to E-box motifs (5'-CANNTG-3') in the promoters of target genes, such as CDH1, and recruiting co-repressors like C-terminal binding protein (CtBP) or histone deacetylases (HDACs). It can also act as an activator by recruiting co-activators like p300 or PCAF (Nature Reviews Cancer, 2013; UniProt, 2024).