Fig. 7
From: Metabolic impairment of non-small cell lung cancers by mitochondrial HSPD1 targeting
Mitochondrial metabolism influences NSCLC cells response to KHS101. A) Scheme showing the genome-wide CRISPR-Cas9 screening platform employed to identify KHS101 resistance genes. B) Gene ontology (GO) analysis of the top 20 candidates identified from the knockout screen in cells after treatment with KHS101. GO was performed with the cellular component 2017b gene set library in Enrichr tool. C) Dose–response curves to KHS101 (normalized to DMSO control) of A549 cells overexpressing two gRNAs to knockout COX5B, compared to parental A549. Points are averages of replicates ± SD. IC50 values (μM) are shown. P-values are from two-way ANOVA. * < 0.05. D) Bar graphs showing quantification of basal respiration, indicative glycolysis and ATP-linked respiration of A549 COX5B knockout cells compared to parental cells. Bars are average of replicates ± SD. P-values are from unpaired t-test. *** < 0.001, **** < 0.0001. E) Dose–response curves (normalized to DMSO control) of A549, H460 and H1299 cells in presence of glycolysis inhibitor 2-deoxy-D-glucose (2-DG). Points are average values of replicates ± SD. IC50 values (μM) are shown. P-values are from two-way ANOVA. **** < 0.0001. F) Schematic representation of the metabolic alterations that occur in NSCLC cells upon HSPD1 loss