PO-178 WDR5 promotes metastasis dissemination in breast cancer

IntroductionThe core subunit of the COMPASS-like complex, WD Repeat Domain 5 (WDR5) has a prominent role in cell self-renewal, reprogramming and Epithelial-to-Mesenchymal transition (EMT) in different tumour types. We have identified WDR5 as an epigenetic target in in vivo and in vitro shRNA screenings performed in MCF10DCIS.com (from now MCF10DCIS) breast cancer (BC) cells. Here, we show that WDR5 can regulate metastasis dissemination in BC by stimulating TGFB-induced EMT.Material and methodsMCF10DCIS and MDAMB231 cells and six metastatic PDXs were used for in vivo and in vitro studies. Cells were transduced to silence WDR5 (shWDR5) or a neutral control (shLuc). Transcriptomic profiles were evaluated by RNA-seq in shLuc and shWDR5 PDXs and MCF10DCIS cells. Differentially expressed genes (DEGs) were identified using Log2FC>|0.6| and FDR