Nuclear envelope rupture and repair during cancer cell migration

Menées in vitro et in vivo, ces deux études mettent en évidence les déformations subies par l'enveloppe du noyau des cellules cancéreuses, ainsi que des mécanismes de réparation de ces déformations, lors de la migration des cellules à travers le micro-environnement tumoral

Résumé en anglais

During cancer metastasis, tumor cells penetrate tissues through tight interstitial spaces, requiring extensive deformation of the cell and its nucleus. Here, we investigated mammalian tumor cell migration in confining microenvironments in vitro and in vivo. Nuclear deformation caused localized loss of nuclear envelope (NE) integrity, which led to the uncontrolled exchange of nucleo-cytoplasmic content, herniation of chromatin across the NE, and DNA damage. The incidence of NE rupture increased with cell confinement and with depletion of nuclear lamins, NE proteins that structurally support the nucleus. Cells restored NE integrity using components of the endosomal sorting complexes required for transport-III (ESCRT-III) machinery. Our findings indicate that cell migration incurs substantial physical stress on the NE and its content, requiring efficient NE and DNA damage repair for cell survival.