Genome-wide cooperation of the EMT inducer ZEB1 with AP-1 and YAP in aggressive breast cancer

Cancer is one of the leading causes of death worldwide and its incidence is still rising. Decades of cancer research have brought major progress in therapeutic interventions for cancer patients. Yet, for many often especially aggressive cancer types, no specific treatment options exist and, in the vast majority of cases, metastatic spread of the primary tumour still represents a terminal illness. The epithelial to mesenchymal transition (EMT) is one process that promotes aggressive cancer behaviour and metastasis. EMT is controlled by a core set of transcription factors, one of which is the zinc-finger domain protein ZEB1. ZEB1 is primarily described as a powerful transcriptional repressor of epithelial differentiation genes. However, ZEB1 can also directly activate tumour promoting target genes by cooperating with different co-factors, e. g. with the Hippo pathway effector YAP. The present work aimed to generate a comprehensive picture of ZEB1-mediated transcriptional regulation on a genome-wide scale in aggressive breast cancer.