Co-dependency for MET and FGFR1 in basal triple negative breast cancers

Triple-negative breast cancer (TNBC) is a heterogeneous disease that lacks both effective patient stratification strategies and therapeutic targets. In the present study, we assay tumour-initiating cells (TICs) properties, using established Met-dependent transgenic mouse models of TNBC, breast cancer cell lines and, patient-derived xenografts, to directly investigate the role of Met in tumour initiation and identify FGFR1 signaling as a key convergent pathway with Met for the maintenance of TICs. To understand the events that occur in TICs upon inhibition of Met and FGFR1, we performed gene expression profiling by RNA-Sequencing of RNA prepared from tumoursphere from 3 independent MMTV-Metmt;Trp53fl/+;Cre derived spindloid tumour cell lines (A1005, A1129, A1471) following treatment with Met or FGFR inhibitor alone (Crizotinib or PD173074, respectively), or in combination for 24h. Overall design: Differential gene expression profile following drugs treatment of tumoursphere from 3 independent MMTV-Metmt;Trp53fl/+;Cre derived spindloid tumour cell lines (A1005, A1129, A1471) following treatment with Met or FGFR inhibitor alone (Crizotinib or PD173074, respectively), or in combination for 24h, by RNA-Sequencing using a NextSeq500 sequencer (Illumina).