Empirical single-cell tracking and cell-fate simulation reveal dual roles of p53 in tumor suppression

The tumor suppressor p53 regulates various stress responses via increasing its cellular levels. The lowest p53 levels occur in unstressed cells; however, the impact of these low levels on cell integrity remains unclear. To address the impact, we used empirical single-cell tracking of p53-expressing and silenced cells, and developed a fate-simulation algorithm. Here we show that p53-silenced cells underwent more frequent cell death and cell fusion, which further induced multipolar cell division to generate aneuploid progeny. Those results suggest that the low levels of p53 in unstressed cells indeed have a role to maintain the integrity of a cell population. Results of a cell-fate simulation that provides a flexible and dynamic virtual culture space confirmed that these aneuploid progeny could propagate. However, p53-silenced cells were unable to propagate in a virtual cell population that was mainly comprised of p53-expressing cells, supporting the notion that p53 acts as a tumor suppre...