Genome–wide binding of transcription factor ZEB1 in triple‐negative breast cancer cells

Zinc finger E‐box binding homeobox 1 (ZEB1) is a transcriptional regulator involved in embryonic development and cancer progression. ZEB1 induces epithelial‐mesenchymal transition (EMT). Triple–negative human breast cancers express high ZEB1 mRNA levels and exhibit features of EMT. In the human triple–negative breast cancer cell model Hs578T, ZEB1 associates with almost 2,000 genes, representing many cellular functions, including cell polarity regulation (DLG2 and FAT3). By introducing a CRISPR‐Cas9‐mediated 30 bp deletion into the ZEB1 second exon, we observed reduced migratory and anchorage‐independent growth capacity of these tumor cells. Transcriptomic analysis of control and ZEB1 knockout cells, revealed 1,372 differentially expressed genes. The TIMP metallopeptidase inhibitor 3 and the teneurin transmembrane protein 2 genes showed increased expression upon loss of ZEB1, possibly mediating pro‐tumorigenic actions of ZEB1. This work provides a resource for regulators of cancer progression that function under the transcriptional control of ZEB1. The data confirm that removing a single EMT transcription factor, such as ZEB1, is not sufficient for reverting the triple–negative mesenchymal breast cancer cells into more differentiated, epithelial‐like clones, but can reduce tumorigenic potential, suggesting that not all pro‐tumorigenic actions of ZEB1 are linked to the EMT.