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Structural centrosome aberrations promote non‐cell‐autonomous invasiveness
Centrosomes are the main microtubule‐organizing centers of animal cells. Although centrosome aberrations are common in tumors, their consequences remain subject to debate. Here, we studied the impact of structural centrosome aberrations, induced by deregulated expression of ninein‐like protein (NLP)...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5920242/ https://www.ncbi.nlm.nih.gov/pubmed/29567643 http://dx.doi.org/10.15252/embj.201798576 |
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author | Ganier, Olivier Schnerch, Dominik Oertle, Philipp Lim, Roderick YH Plodinec, Marija Nigg, Erich A |
author_facet | Ganier, Olivier Schnerch, Dominik Oertle, Philipp Lim, Roderick YH Plodinec, Marija Nigg, Erich A |
author_sort | Ganier, Olivier |
collection | PubMed |
description | Centrosomes are the main microtubule‐organizing centers of animal cells. Although centrosome aberrations are common in tumors, their consequences remain subject to debate. Here, we studied the impact of structural centrosome aberrations, induced by deregulated expression of ninein‐like protein (NLP), on epithelial spheres grown in Matrigel matrices. We demonstrate that NLP‐induced structural centrosome aberrations trigger the escape (“budding”) of living cells from epithelia. Remarkably, all cells disseminating into the matrix were undergoing mitosis. This invasive behavior reflects a novel mechanism that depends on the acquisition of two distinct properties. First, NLP‐induced centrosome aberrations trigger a re‐organization of the cytoskeleton, which stabilizes microtubules and weakens E‐cadherin junctions during mitosis. Second, atomic force microscopy reveals that cells harboring these centrosome aberrations display increased stiffness. As a consequence, mitotic cells are pushed out of mosaic epithelia, particularly if they lack centrosome aberrations. We conclude that centrosome aberrations can trigger cell dissemination through a novel, non‐cell‐autonomous mechanism, raising the prospect that centrosome aberrations contribute to the dissemination of metastatic cells harboring normal centrosomes. |
format | Online Article Text |
id | pubmed-5920242 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-59202422018-05-03 Structural centrosome aberrations promote non‐cell‐autonomous invasiveness Ganier, Olivier Schnerch, Dominik Oertle, Philipp Lim, Roderick YH Plodinec, Marija Nigg, Erich A EMBO J Articles Centrosomes are the main microtubule‐organizing centers of animal cells. Although centrosome aberrations are common in tumors, their consequences remain subject to debate. Here, we studied the impact of structural centrosome aberrations, induced by deregulated expression of ninein‐like protein (NLP), on epithelial spheres grown in Matrigel matrices. We demonstrate that NLP‐induced structural centrosome aberrations trigger the escape (“budding”) of living cells from epithelia. Remarkably, all cells disseminating into the matrix were undergoing mitosis. This invasive behavior reflects a novel mechanism that depends on the acquisition of two distinct properties. First, NLP‐induced centrosome aberrations trigger a re‐organization of the cytoskeleton, which stabilizes microtubules and weakens E‐cadherin junctions during mitosis. Second, atomic force microscopy reveals that cells harboring these centrosome aberrations display increased stiffness. As a consequence, mitotic cells are pushed out of mosaic epithelia, particularly if they lack centrosome aberrations. We conclude that centrosome aberrations can trigger cell dissemination through a novel, non‐cell‐autonomous mechanism, raising the prospect that centrosome aberrations contribute to the dissemination of metastatic cells harboring normal centrosomes. John Wiley and Sons Inc. 2018-03-22 2018-05-02 /pmc/articles/PMC5920242/ /pubmed/29567643 http://dx.doi.org/10.15252/embj.201798576 Text en © 2018 The Authors. Published under the terms of the CC BY NC ND 4.0 license This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Articles Ganier, Olivier Schnerch, Dominik Oertle, Philipp Lim, Roderick YH Plodinec, Marija Nigg, Erich A Structural centrosome aberrations promote non‐cell‐autonomous invasiveness |
title | Structural centrosome aberrations promote non‐cell‐autonomous invasiveness |
title_full | Structural centrosome aberrations promote non‐cell‐autonomous invasiveness |
title_fullStr | Structural centrosome aberrations promote non‐cell‐autonomous invasiveness |
title_full_unstemmed | Structural centrosome aberrations promote non‐cell‐autonomous invasiveness |
title_short | Structural centrosome aberrations promote non‐cell‐autonomous invasiveness |
title_sort | structural centrosome aberrations promote non‐cell‐autonomous invasiveness |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5920242/ https://www.ncbi.nlm.nih.gov/pubmed/29567643 http://dx.doi.org/10.15252/embj.201798576 |
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