KLF5-driven G6PD protects lung squamous cell carcinoma from ferroptosis by sustaining mitochondrial homeostasis and SLC7A11-dependent cystine uptake.
A KLF5-G6PD-SLC7A11 axis is identified as a critical metabolic safeguard against ferroptosis in LUSC, and targeting G6PD disrupts mitochondrial homeostasis, enhances mitophagy-dependent oxidative stress, and sensitizes tumors to ferroptotic therapy, highlighting a promising therapeutic strategy for LUSC.