A functional genomic screen in vivo identifies CEACAM5 as a clinically relevant driver of breast cancer metastasis

PDX lung metastasis signatures identify genes de-regulated in metastases. a Schematic representation of MPF tumors and lungs metastases isolated for RNAseq. b Principal component analyses (PCAs) from RNAseq data generated from MFP tumors and lung metastases used in this study. Each data point represents one sample from an individual mouse. c GSEA pathway analysis on the enriched lung metastasis signature (P2); the top 5 down (blue)- and up (red)regulated processes are shown. NES, normalized enrichment score. Boxes indicate FDR <0.1 for statistical significance. Enrichment plots for epithelial mesenchymal transition (EMT) and TGF-β signaling for P0 and P2 are shown in the right-hand panel. p？<？0.001 for EMT and TGF-β signaling at P0 and P2. d qRT-PCR analysis of vimentin expression in BC3_A2 MFP tumors and metastatic subpopulations isolated from lung. Paired t-tests, p？=？0.02 for P0 lung, p？<？0.001 for P2 lung. Each data point represents one mouse. Error bars represent SEM of biological replicates. See also Supplementary Fig. 2. e IHC staining was performed on the indicated tissue sections using an antibody recognizing the human-specific form of vimentin. Scale bars indicate 100？μm. f Waterfall plot showing expression of EMT genes in P0 and P2 lung metastases compared with corresponding MFP tumors. p-values are provided in Supplementary Table 1. Samples from at least three independent mice were included for RNAseq analyse