Fig. 3

The key mitotic catastrophe, necroptosis and ferroptosis pathways in triple-negative breast cancer (TNBC). a DNA damage inhibits checkpoint kinase 1 (chk1) and cyclin-dependent kinase (CDK) 2 targets and then inhibits the recovery of cell cycle checkpoints, resulting in mitotic catastrophe. The rad3-related protein (ATR)-chk1 signaling pathway is activated in the absence of G2 checkpoints, restores S/G2 and G2/M cell cycle checkpoints and avoids the production of mitotic catastrophe. PI3K-like kinase (PIKK)/mammalian target of rapamycin (mTOR) inhibitors cause the accumulation of single-stranded deoxyribonucleic acid (ssDNA), replication catastrophe and mitotic failure, and ultimately lead to mitotic catastrophe. Polo-like kinase 1 (Plk1)-interacting checkpoint helicase (PICH) depletion can also lead to mitotic catastrophe. Bromodomain and extraterminal protein (BET) inhibitors eventually cause mitotic catastrophe by inhibiting B-cell lymphoma-extra-large (Bcl-xL). The production of the above mitotic catastrophe will eventually cause the death of TNBC cells; b Aquaporin1 (AQP1) can inhibit receptor-interacting protein (RIPK) 1/RIPK3/mixed lineage kinase domain-like (MLKL)-mediated necroptosis by binding to the D324 site of RIPK1. The fas associated via death domain (FADD)/TNFRSF1A associated via death domain (TRADD) complex depends on both RIPK1/caspase-8-mediated apoptosis and RIPK1/RIPK3/MLKL-mediated necroptosis. The production of the above necroptosis will eventually cause the death of TNBC cells; c Zn protoporphyrin IX (Znpp) inhibits the accumulation of unstable iron pools by inhibiting HO-1, reduces reactive oxygen species (ROS) levels and reduces ferroptosis caused by lipid peroxidation. Cystine enters and exits the cell membrane through solute carrier family 7 member 11 (SLC7A11)/solute carrier family 3 member 2 (SLC3A2), converts to cysteine, causes glutathione (GSH) levels to rise, activates Glutathione peroxidase 4 (GPX4) and inhibits ferroptosis caused by lipid peroxidation. The production of the above ferroptosis will eventually cause the death of TNBC cells