p53 Suppresses Metabolic Stress-Induced Ferroptosis in Cancer Cells

• DOI: 10.1016/j.celrep.2017.12.077
• Publication Date: 2018-01-29T14:31:12Z
• Authors: Amy Tarangelo; Leslie Magtanong; Kathryn T. Biegin...; Yang Li; Jiangbin Ye; Laura D. Attardi; Scott J. Dixon
• Keywords: p53; reactive oxygen species; cystine; Cyclin-Dependent Kinase Inhibitor p21; 0301 basic medicine; QH301-705.5; Apoptosis; Glutathione; ferroptosis; 3. Good health; Mice; 03 medical and health sciences; cell death; Cell Line, Tumor; Neoplasms; cancer; Animals; Humans; glutathione; Biology (General); Tumor Suppressor Protein p53; Reactive Oxygen Species; metabolism

How cancer cells respond to nutrient deprivation remains poorly understood. In certain cells, of cystine induces a non-apoptotic, iron-dependent form cell death termed ferroptosis. Recent evidence suggests that ferroptosis sensitivity may be modulated by the stress-responsive transcription factor and canonical tumor suppressor protein p53. Using CRISPR/Cas9 genome editing, small-molecule probes, high-resolution, time-lapse imaging, we find stabilization wild-type p53 delays onset in response deprivation. This delay requires transcriptional target CDKN1A (encoding p21) is associated with both slower depletion intracellular glutathione reduced accumulation toxic lipid-reactive oxygen species (ROS). Thus, p53-p21 axis help cope metabolic stress induced delaying non-apoptotic death.