Fig. 1.

Death effector domain-containing DNA-binding protein (DEDD) upregulation confers a vulnerability to epidermal growth factor receptor/human epidermal growth factor receptor 2 (EGFR/HER2) inhibitor. a Schematic representation of the synthetic lethal bar-coded short hairpin RNA (shRNA) drop-out screen using triple-negative breast cancer (TNBC) cell line HCC1806 with the EGFR inhibitor lapatinib (LAP) treatment. b Bar-coded shRNAs enriched or depleted in the LAP-treated HCC1806 cells compared with dimethyl sulfoxide (DMSO)-treated cells. The bar-coded shRNAs of the top 200 depleted genes in LAP-treated cells were considered as drop-out hits (MAGeCK method, colored yellow). c Genetic and epigenetic alterations of the top 10 genes among top 200 depleted genes that are upregulated in estrogen-negative/progesterone receptor-negative/HER2 (ER−/PR−/HER2) normal tumors (n = 152) found within the Cancer Genome Atlas (TCGA). d Segmented view of the copy-number changes of DEDD, ABCB10, UAP1, KCNJ9, and PSAT1 in TCGA breast-invasive carcinoma tumors. e Genome alteration frequency plot of top 10 cancer studies with DEDD, ABCB10, UAP1, KCNJ9, and PSAT1 alterations across 164 studies in cBioPortal. f Cell counting assay validating knockdown of DEDD sensitizes TNBC cells to LAP treatment (error bars: means ± s.e.m). Cells were normalized to DMSO control group in each shRNA or PLKO.1 (Control) group. All quantitative data were generated from a minimum of three replicates. P values were derived from one-way analysis of variance (ANOVA) with Dunnett’s multiple comparison test comparing different shRNAs to the PLKO.1 group