Study on the role of TIGAR in regulating mitochondrial function and inhibiting pyroptosis of breast cancer cells.

Insufficient immunogenic cell death (ICD) within tumors, particularly the difficulty in inducing pyroptosis, represents a critical factor contributing to treatment resistance, recurrence, and metastasis in triple-negative breast cancer (TNBC). Recent investigations into the roles of pyroptosis-related proteins in breast cancer have laid a foundation for developing therapeutic strategies centered on pyroptosis induction. However, clinical approaches that effectively trigger pyroptosis for cancer treatment remain unavailable, highlighting the urgent need to identify additional pyroptosis-related proteins and elucidate their functional mechanisms. This study revealed that TP53-induced glycolysis and apoptosis regulator (TIGAR) inhibited nigericin-induced pyroptosis in TNBC cells, whereas knockdown of TIGAR significantly augmented the level of pyroptosis. Mechanistically, TIGAR suppressed nigericin-triggered pyroptosis by preserving mitochondrial function and attenuating intracellular reactive oxygen species (ROS) accumulation. These findings supported the first evidence of TIGAR's regulatory role in the pyroptosis pathway in TNBC cells, offering a theoretical basis for targeting TIGAR as a novel therapeutic strategy for TNBC.