Nuclear Envelope Rupture and Repair During Cancer Cell Migration

Overview

Journal Science

Specialty Science

Date 2016 Mar 26

PMID 27013428

Citations 622

Authors

Celine M Denais

Rachel M Gilbert

Philipp Isermann

Alexandra L McGregor

Mariska Te Lindert

Bettina Weigelin

Patricia M Davidson

Peter Friedl

Katarina Wolf

Jan Lammerding

Affiliations

Soon will be listed here.

Abstract

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 III (ESCRT III) machinery. Our findings indicate that cell migration incurs substantial physical stress on the NE and its content and requires efficient NE and DNA damage repair for cell survival.

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