How LDHB Protects Lung Cancer Cells from Death

Ferroptosis is a type of cell death that cancer cells often avoid, but the reasons behind this in certain cancers driven by the KRAS oncogene are not well understood. Scientists have found that lactate dehydrogenase B (LDHB), a protein involved in energy production, helps KRAS-driven lung cancer cells escape ferroptosis. Unlike its closely related form, LDHA, LDHB has a different role in these cancer cells.Researchers used mouse models and human cancer cell lines to explore this. They discovered that when LDHB is removed, the cells' ability to produce glutathione (GSH), a vital antioxidant, is weakened. This makes the cells more sensitive to treatments that block GSH production or use. As a result, the cells undergo ferroptosis, a process that increases their use of glutamine and oxygen for energy, and generates harmful molecules called mitoROS. Moreover, suppressing LDHB boosts the activity of STAT1, a protein that regulates another protein called SLC7A11. This decreases the cells' ability to make GSH, further weakening their defenses against ferroptosis. This study highlights a new way that LDHB helps cancer cells resist ferroptosis and offers a new strategy for targeting KRAS-driven lung cancer by exploiting its vulnerability to ferroptosis.