Figure 7 from N-Myristoytransferase Inhibition Causes Mitochondrial Iron Overload and Parthanatos in TIM17A-Dependent Aggressive Lung Carcinoma
Year: 2024
Type: other
Abstract: Dependency on TIM17A is a determinant of NMTi sensitivity in lung carcinoma cells. A, TIM17A immunoblotting in the indicated cells treated with 1 μmol/L PCLX-001 (NMTi) for 72 hours. Numbers, band intensity normalized to actin control. B, Boxplot showing CRISPR DepMap Score for LUAD cells (y-axis) estimated using the Chronos algorithm. Negative values suggest decreased cell viability. (KL/K)MUT (HCC44, H460, and H1792) and (KL/K)WT (H522, H1650, and H1437) lung carcinoma cells used in our study are highlighted. C, TIM17A CRISPR Chronos scores (y-axis) plotted against NMTi IC50 (x-axis; Spearman’s Correlation, P = 0.006, ⍴ = −0.43). Axis scales are log-transformed, and the best-fit line (blue) was calculated using a linear model. Gray shading, standard error of the estimate. H460 was added manually based on our calculated IC50 and the publicly available dependency score. D, Cell viability (crystal violet staining) in (KL/K)MUT H1792 and (KL/K)WT H522 lung carcinoma cells transfected with a TIM17-targeting siRNA pool or a non-targeting control. Bar: average; error bars, SEM. One representative experiment from three independent experiments with similar results. ***, P = 0.0009 (Student t test). Bottom, TIM17A immunoblotting of the samples above. E, Colony assays of (KL/K)MUT H460 and (KL/K)WT H522 expressing Tet-inducible TIM17A or control non-targeting shRNA growing in the presence or absence of Dox. Top, Representative images. Bottom, TIM17A immunoblotting of lysates from the cells used for colony assays. GAPDH, loading control.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4400979786