ZEB1

Overview

ZEB1 (Zinc finger E-box binding homeobox 1) is a transcriptional repressor that drives epithelial-to-mesenchymal transition (EMT) by silencing E-cadherin (CDH1) and other epithelial markers. ZEB1 is negatively regulated by the miR-200 family of microRNAs, forming a double-negative feedback loop that controls cell plasticity. In the NCI-60 cancer cell line panel, ZEB1 expression is strongly inversely correlated with CDH1 (E-cadherin) expression, confirming its role as a master EMT regulator across multiple cancer types.

Alterations observed in the corpus

  • ZEB1 identified as a transcriptional repressor of CDH1 (E-cadherin) in the NCI-60 CellMiner pharmacogenomics analysis; correlation coefficient r = -0.63 between ZEB1 and CDH1 expression across NCI-60 cell lines PMID:22802077
  • EMT transcription factor upregulated in GBC cells downstream of SEMA7A/ITGB1/AKT1/EP300 signaling; p300 occupancy and H3K27ac at the ZEB1 promoter increased by recombinant SEMA7A, abrogated by p300 S1834A mutation. PMID:24997986

Cancer types (linked)

  • Multiple cancer types (NCI-60 panel): ZEB1 expression inversely correlated with CDH1/E-cadherin across diverse cancer cell lines; ZEB1 high-expressing lines exhibit EMT phenotype PMID:22802077

Co-occurrence and mutual exclusivity

  • ZEB1 expression anti-correlated with CDH1 (r = -0.63) across NCI-60 cell lines, consistent with direct transcriptional repression PMID:22802077
  • ZEB1 co-regulates EMT alongside SNAI2, ZEB2, and TWIST1 (all repressors of CDH1) and is negatively regulated by the miR-200 microRNA family PMID:22802077

Therapeutic relevance

  • ZEB1-driven EMT may contribute to drug resistance; the NCI-60 CellMiner platform enables correlation of ZEB1/CDH1 status with drug sensitivity patterns across 20,000+ compounds PMID:22802077

Open questions

  • Whether ZEB1 expression levels predict specific drug sensitivity or resistance in patient tumors (vs. cell lines) remains to be validated in the corpus.

Sources

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