Fig. 2

ITGB3-NFkB signaling contributes to acquisition of chemoresistance in mesenchymal lung cancer cell a The genes strongly associated with chemoresistance and increased expression in TD compared to A549 cell. Known EMT-genes are marked in red. b Distribution of the number of ITGB3 vulnerable cells (dependency score < − 1) belonging to the sensitive (S) and resistant (R) group for 32 chemotherapeutic and 20 targeted drugs. (P-value by t-test). c Immunoblotting analysis for cleaved PARP (C.PARP), cleaved caspase 3 and 9 (C.Caspase3 and 9) of TD shCont, shβ #3 and shβ #4 after doxorubicin (Doxo) treatment at indicative days d Immunoblotting analysis for cleaved caspase 3 and 9 (C.Caspase3 and 9) after Etoposide (ETO, 80 μM) treatment with or without transient transfection of ITGB3 in A549 e Enriched pathways (hypergeometric test, q-value < 0.1) and the median hazard ratio of the member genes in each pathway among the down-regulated genes by ITGB3 depletion. Hazard ratio is calculated using TCGA LUAD patient dataset, and cancer signaling pathways are marked in red. f Expression change of NF-κB signaling genes (z-score, normalized log2 fold change) g Fluorescent microscopic images for p65 (Green) in A549 and TD cells. DAPI (Blue) for nuclear counterstaining, (The scale bars: 50 μm) h Immunoblotting analysis for IκB and acetylated p64 at lysine 221 (K221) in TD (shCont) and ITGB3 KD cells, β-actin for equal loading control i Luciferase reporter activity for NF-κB activity in TD (shCont) and ITGB3 KD cells (shβ#3 or shβ#4) j Immunoblotting analysis for p65, cleaved PARP, caspase 3 and 9 (C.PARP, C.Caspase3 and 9) after p65 knockdown with siRNAs (#2 or #3)