Nuclear envelope rupture and repair during cancer cell migration

During cancer metastasis, tumor cells penetrate tissues through tight interstitial spaces, which requires 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…

• NS
  National Science Foundation

  Awards: 1428922, DGE-1144153, CBET-1254846, ECCS-15420819
• NY
  New York Stem Cell Foundation

  Award: CO29155
• NO
  Nederlandse Organisatie voor Wetenschappelijk Onderzoek

  Awards: NWO-VIDI 917.10.364, NWO-VICI 918.11.626
• NI
  National Institutes of Health

  Awards: R01 HL082792, S10OD018516, R01 NS059348
• NC
  National Cancer Institute