Fig. 3: SUMO2-K11la counteracts ferroptosis in LUAD.

a, b Ferroptosis inhibitors ferrostatin-1 (Ferr-1, 10 μM) and deferoxamine (DFO, 10 μM) reversed K11R-driven cell death in LUAD cells, while apoptosis inhibitor Z-VAD-FMK (10 μM) and necroptosis inhibitor Necrosulfonamide (Necro, 10 μM) had no significant effect. c Relative viability of A549 Ctrl and K11R cells following treatment with varying concentrations of RSL3 (48 h), IKE (72 h), or CDDP (72 h) with or without concurrent incubation with NALA (5 mM). d–f Quantification of ferroptosis-associated biomarkers demonstrated the ferroptosis-promoting effect of K11R mutation: lipid-ROS were measured via BODIPY-C11 fluorescence probes (d), MDA levels were assessed by thiobarbituric acid assay (e), and cellular redox status was determined by GSH/GSSG ratio (f). g, h Transmission electron microscopy revealed pronounced mitochondrial damage (cristae disappearance and mitochondrial shrinkage) in K11R cells, which is not significantly affected by NALA supplementation. Scale bars, 5 μm. i, j Immunohistochemistry of LUAD patient tissues demonstrated an inverse correlation between SUMO2-K11la levels and lipid peroxidation marker 4-hydroxynonenal (4-HNE). Scale bars, 200 μm. k, l High SUMO2-K11la expression predicted reduced overall survival in 140 LUAD patients (k) and 45 CDDP-treated patients (l). Statistical analysis was performed using one-way ANOVA, and results were presented as mean ± SD.