Sublethal cytochrome c release generates drug-tolerant persister cells

• Published in: Cell Vol. 185; no. 18; pp. 3356 - 3374.e22
• Main Authors: Kalkavan, Halime, Chen, Mark J., Crawford, Jeremy C., Quarato, Giovanni, Fitzgerald, Patrick, Tait, Stephen W.G., Goding, Colin R., Green, Douglas R.
• Format: Journal Article
• Language: English
• Published: United States 01.09.2022
• Subjects: Animals; Apoptosis; cancer therapy; Carrier Proteins; caspases; Caspases - metabolism; cytochrome c; Cytochromes c - metabolism; Drug Resistance, Neoplasm; ferroptosis; Humans; membrane permeability; metastasis; Mice; mitochondria; Mitochondria - metabolism; Neoplasms - drug therapy; phenotype; stress response; ferroptosis; GPX4; HRI; ATF4; Bcl-2 family; persister integrated stress response

Drug-tolerant persister cells (persisters) evade apoptosis upon targeted and conventional cancer therapies and represent a major non-genetic barrier to effective cancer treatment. Here, we show that cells that survive treatment with pro-apoptotic BH3 mimetics display a persister phenotype that inclu...