Katarina Wolf (photo up), theme Nanomedicine and Bettina Weigelin, theme Cancer development and immune defence, both from the Dept. of Cell Biology, together with the team of Jan Lammerding at Cornell University, Ithaca, USA identified transient nuclear envelope rupture and repair processes in actively moving cancer cells, in vitro and in vivo. They found that strong deformation of the nucleus during movement through tight space leads to the transient leakage of nuclear content into the cytosol and rapid repair through the ESCRT machinery, but DNA damage.
The RIMLS team applied advanced microscopy to monitor invading cancer cells “in the act” in 3D tissue models in vitro and growing tumors in live mice to clarify that the nucleus is vulnerable in up to 70% of the cells, depending on the tissue density, but that most damage is repaired within an hour. The collaborators at Cornell worked out the exact mechanical conditions, using synthetic microdevices and identified the ‘endosomal sorting complexes required for transport-III (ESCRT-III) complex as main route for rapid repair of nuclear rupture. By dual-inhibition of both, DNA damage and nuclear envelope repair pathways, tumor cell apoptosis was induced and may therefore represent a weakness of cancer cells for therapeutic targeting.
This study is published in Science, back-to-back with similar work on immune cells by a French team:
Nuclear envelope rupture and repair during cancer cell migration. Science, 2016
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