WDR5 regulates EMT and metastasis in breast cancer by activating TGFB pathway [ChIP-seq]

The core subunit of the COMPASS-like complex, WD Repeat Domain 5 (WDR5) has a prominent role in reprogramming and Epithelial-to-Mesenchymal transition (EMT) in different tumor types. Our evidences support a model in which WDR5 is prominent for EMT and metastasis dissemination in breast cancer patient-derived xenografts and cell lines. Moreover, WDR5 silencing abrogates TGFB pathway activation and reverts mesenchymal into epithelial phenotype, by inhibiting transcription of main master regulators of EMT (CDH2, TWIST1, SNAI1, SNAI2 and ZEB1). Our data suggest that WDR5 inhibition may be a successful approach to prevent progression of metastatic BC. Overall design: Chromatin from MCF10DCIS.com breast cancer cell line was immunoprecipitated with anti-WDR5 and anti-H3K4me3 antibody and subjected to multiparallel sequencing. Experiments were carried out in shLuc (control) and WDR5 silenced cells.