Mutant p53 protects triple-negative breast adenocarcinomas from ferroptosis in vivo

• DOI: 10.1126/sciadv.adk1835
• Publication Date: 2024-02-14T18:58:58Z
• Authors: Denada Dibra; Shunbin Xiong; Sydney M. Moyer; Adel K. El-Naggar; Yuan Qi; Xiaoping Su; Elisabeth K. Kong; Anil Korkut; Guillermina Lozano
• Keywords: Triple-negative breast cancer; GPX4

The TP53 tumor suppressor gene is mutated early in most of the patients with triple-negative breast cancer (TNBC). frequent alterations are missense mutations that contribute to aggressiveness. Here, we used an autochthonous somatic TNBC mouse model, which mutant p53 can be toggled on and off genetically while leaving microenvironment intact wild-type for identify physiological dependencies p53. In TNBCs develop this deletion two different hotspot p53R172H p53R245W mutants triggers ferroptosis vivo, a cell death mechanism involving iron-dependent lipid peroxidation. Mutant protects cells from inducers, inhibitors reverse effects loss vivo. Single-cell transcriptomic data revealed undergoing through NRF2-dependent regulation Mgst3 Prdx6 , encode glutathione-dependent peroxidases detoxify peroxides. Thus, ferroptotic death.