Publication Date:
2016-03-26
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4833568/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4833568/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Denais, Celine M -- Gilbert, Rachel M -- Isermann, Philipp -- McGregor, Alexandra L -- te Lindert, Mariska -- Weigelin, Bettina -- Davidson, Patricia M -- Friedl, Peter -- Wolf, Katarina -- Lammerding, Jan -- R01 HL082792/HL/NHLBI NIH HHS/ -- R01 NS059348/NS/NINDS NIH HHS/ -- S10OD018516/OD/NIH HHS/ -- U54 CA143876/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2016 Apr 15;352(6283):353-8. doi: 10.1126/science.aad7297. Epub 2016 Mar 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Nancy E. and Peter C. Meinig School of Biomedical Engineering and Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA. ; Department of Cell Biology, Radboud University Medical Center, Nijmegen, Netherlands. ; Department of Cell Biology, Radboud University Medical Center, Nijmegen, Netherlands. Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Cancer Genomics Center, Netherlands (CGC.nl). ; Nancy E. and Peter C. Meinig School of Biomedical Engineering and Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA. jan.lammerding@cornell.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27013428" target="_blank"〉PubMed〈/a〉
Keywords:
Cell Line, Tumor
;
*Cell Movement
;
Chromatin/metabolism
;
Cytoplasm/metabolism
;
DNA Damage
;
Endosomal Sorting Complexes Required for Transport/metabolism
;
Humans
;
Lamins/deficiency
;
Neoplasms/metabolism/*pathology
;
Nuclear Envelope/metabolism/*pathology
;
Stress, Mechanical
;
*Tumor Microenvironment
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
