What is it about?

In response to chemotherapy, radiation, or other toxins, damaged cells commit suicide by activating biological machines called enzymes that chop up cellular components. But in response to a given toxin, some cells die while others live. What makes the difference? We made cells in which we could deliver and measure precise numbers of active enzymes to ask whether it is how many there are or how quickly they accumulate that determines cell death vs survival. We found that neither perfectly predicts the outcome. Rather, the state of the cell contributes to the decision. Cells given another type of stress were more likely to die even in the presence of the same number of active enzymes, than cells maintained under optimal conditions. These findings show that multiple signals together determine life vs death.

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Why is it important?

In response to chemotherapy or radiation treatment, many cancer cells die and patients often achieve remission. However, frequently some cells escape and cause relapse. Cells can escape death either due to random mutations that render them insensitive to the treatment or by recovering from the treatment. This work suggests that some of the variation in cellular responses to treatment might result from differences in their states prior to treatment, such as the nutrient or oxygen conditions. Further understanding these mechanisms may improve cell killing and limit relapse.

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This page is a summary of: Cell survival following direct executioner-caspase activation, Proceedings of the National Academy of Sciences, January 2023, Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.2216531120.
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