Glucose starvation induces NADPH collapse and disulfide stress in SLC7A11high cancer cells

摘要

Malignant cells are known to exhibit increased glucose uptake compared to normal cells. Besides providing energy “currency” ATP, glucose also contributes to intracellular redox maintenance through generating the universal cellular reduction “currency” reduced nicotinamide adenine dinucleotide phosphate (NADPH) primarily via the pentose phosphate pathway (PPP), as well as donates carbon intermediates for the biosynthesis of diverse macromolecules. Glucose starvation induces rapid cell death in some cancer cell lines whereas other cancer cell lines are resistant to glucose deprivation. However, the genetic determinants underlying differential sensitivities to glucose starvation–induced cell death in cancer cells remain incompletely understood.