Effect of G6PD loss on gene expression in LKB1 deficient KRAS-driven lung tumor
Cancer cells heavily rely on nicotinamide adenine dinucleotide phosphate (NADPH) to counteract oxidative stress and facilitate reductive biosynthesis. One crucial route for NADPH production operates through the oxidative pentose phosphate pathway, with a pivotal step at glucose-6-phosphate dehydrogenase (G6PD). This study delves into the repercussions of G6PD ablation on the development of lung tumors driven by the KRAS oncogene and deficient in LKB1 (KL). The research involved comparing the growth of KL lung tumors with or without G6PD, revealing a significant inhibition of KL lung tumor growth upon G6PD loss. Subsequently, RNA-seq analysis was employed to identify the alterations in gene expression following G6PD deletion, providing insights into the underlying mechanisms. Overall design: To tumor-specificly knock out G6PD in KL lung tumor, we crossed KrasG12D;Lkb1flox/flox mice with G6pdflox/flox mice to generate G6pdflox/flox;KrasLSL-G12D/+;Lkb1flox/flox mice and G6pdWT;KrasLSL-G12D/+;Lkb1flox/flox mice. Following this, Lenti-cre infection was utilized to induce tumor formation and simultaneously delete Lkb1/G6pd. After 12 weeks of tumor induciton, lung tumors were dissected from the mice, RNA-Seq then was employed  to analyze the gene expression in KL lung tumors, comparing those with and without G6PD.