Mitosis sets nuclear homeostasis of cancer cells under confinement

During their life, mammalian cells are subjected to numerous mechanical constraints, especially in pathological contexts such as cancer. Recent studies have highlighted the central role of the nucleus in sensing mechanical cues, but they only focus on short periods of time, and so far, whether cells can adapt to prolonged confinement remains unknown. Here, we reveal the unsuspected role of mitosis in the long-term adaptation of nuclei to prolonged uniaxial confinement. For the colorectal cancer cell line investigated, following the first confined cell division, a new homeostatic state was reached by nuclei: they were smaller, and had reset the tension of their envelope. This adaptation through mitosis relied both on the nuclear tension sensor cPLA2 and the contractility machinery. We report for the first time a mechano-adaptation during mitosis, a process that could be crucial to adapt to stresses in the tumor microenvironment. We therefore anticipate that our work could provide new insight into cancer cell plasticity and cancer relapse.