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Constricted migration increases DNA damage and independently represses cell cycle
Cell migration through dense tissues or small capillaries can elongate the nucleus and even damage it, and any impact on cell cycle has the potential to affect various processes including carcinogenesis. Here, nuclear rupture and DNA damage increase with constricted migration in different phases of...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232975/ https://www.ncbi.nlm.nih.gov/pubmed/29742017 http://dx.doi.org/10.1091/mbc.E18-02-0079 |
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author | Pfeifer, Charlotte R. Xia, Yuntao Zhu, Kuangzheng Liu, Dazhen Irianto, Jerome García, Victor M. Morales Millán, Leeza M. Santiago Niese, Brandon Harding, Shane Deviri, Dan Greenberg, Roger A. Discher, Dennis E. |
author_facet | Pfeifer, Charlotte R. Xia, Yuntao Zhu, Kuangzheng Liu, Dazhen Irianto, Jerome García, Victor M. Morales Millán, Leeza M. Santiago Niese, Brandon Harding, Shane Deviri, Dan Greenberg, Roger A. Discher, Dennis E. |
author_sort | Pfeifer, Charlotte R. |
collection | PubMed |
description | Cell migration through dense tissues or small capillaries can elongate the nucleus and even damage it, and any impact on cell cycle has the potential to affect various processes including carcinogenesis. Here, nuclear rupture and DNA damage increase with constricted migration in different phases of cell cycle—which we show is partially repressed. We study several cancer lines that are contact inhibited or not and that exhibit diverse frequencies of nuclear lamina rupture after migration through small pores. DNA repair factors invariably mislocalize after migration, and an excess of DNA damage is evident as pan-nucleoplasmic foci of phosphoactivated ATM and γH2AX. Foci counts are suppressed in late cell cycle as expected of mitotic checkpoints, and migration of contact-inhibited cells through large pores into sparse microenvironments leads also as expected to cell-cycle reentry and no effect on a basal level of damage foci. Constricting pores delay such reentry while excess foci occur independent of cell-cycle phase. Knockdown of repair factors increases DNA damage independent of cell cycle, consistent with effects of constricted migration. Because such migration causes DNA damage and impedes proliferation, it illustrates a cancer cell fate choice of “go or grow.” |
format | Online Article Text |
id | pubmed-6232975 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-62329752018-11-19 Constricted migration increases DNA damage and independently represses cell cycle Pfeifer, Charlotte R. Xia, Yuntao Zhu, Kuangzheng Liu, Dazhen Irianto, Jerome García, Victor M. Morales Millán, Leeza M. Santiago Niese, Brandon Harding, Shane Deviri, Dan Greenberg, Roger A. Discher, Dennis E. Mol Biol Cell Articles Cell migration through dense tissues or small capillaries can elongate the nucleus and even damage it, and any impact on cell cycle has the potential to affect various processes including carcinogenesis. Here, nuclear rupture and DNA damage increase with constricted migration in different phases of cell cycle—which we show is partially repressed. We study several cancer lines that are contact inhibited or not and that exhibit diverse frequencies of nuclear lamina rupture after migration through small pores. DNA repair factors invariably mislocalize after migration, and an excess of DNA damage is evident as pan-nucleoplasmic foci of phosphoactivated ATM and γH2AX. Foci counts are suppressed in late cell cycle as expected of mitotic checkpoints, and migration of contact-inhibited cells through large pores into sparse microenvironments leads also as expected to cell-cycle reentry and no effect on a basal level of damage foci. Constricting pores delay such reentry while excess foci occur independent of cell-cycle phase. Knockdown of repair factors increases DNA damage independent of cell cycle, consistent with effects of constricted migration. Because such migration causes DNA damage and impedes proliferation, it illustrates a cancer cell fate choice of “go or grow.” The American Society for Cell Biology 2018-08-08 /pmc/articles/PMC6232975/ /pubmed/29742017 http://dx.doi.org/10.1091/mbc.E18-02-0079 Text en © 2018 Pfeifer et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License. |
spellingShingle | Articles Pfeifer, Charlotte R. Xia, Yuntao Zhu, Kuangzheng Liu, Dazhen Irianto, Jerome García, Victor M. Morales Millán, Leeza M. Santiago Niese, Brandon Harding, Shane Deviri, Dan Greenberg, Roger A. Discher, Dennis E. Constricted migration increases DNA damage and independently represses cell cycle |
title | Constricted migration increases DNA damage and independently represses cell cycle |
title_full | Constricted migration increases DNA damage and independently represses cell cycle |
title_fullStr | Constricted migration increases DNA damage and independently represses cell cycle |
title_full_unstemmed | Constricted migration increases DNA damage and independently represses cell cycle |
title_short | Constricted migration increases DNA damage and independently represses cell cycle |
title_sort | constricted migration increases dna damage and independently represses cell cycle |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232975/ https://www.ncbi.nlm.nih.gov/pubmed/29742017 http://dx.doi.org/10.1091/mbc.E18-02-0079 |
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