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Senescent stroma induces nuclear deformations in cancer cells via the inhibition of RhoA/ROCK/myosin II-based cytoskeletal tension
The presence of senescent cells within tissues has been functionally linked to malignant transformations. Here, using tension-gauge tethers technology, particle-tracking microrheology, and quantitative microscopy, we demonstrate that senescent-associated secretory phenotype (SASP) derived from senes...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9830950/ https://www.ncbi.nlm.nih.gov/pubmed/36712940 http://dx.doi.org/10.1093/pnasnexus/pgac270 |
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author | Aifuwa, Ivie Kim, Byoung Choul Kamat, Pratik Starich, Bartholomew Agrawal, Anshika Tanrioven, Derin Luperchio, Teresa R Valencia, Angela M Jimenez Perestrelo, Tania Reddy, Karen Ha, Taekjip Philip, Jude M |
author_facet | Aifuwa, Ivie Kim, Byoung Choul Kamat, Pratik Starich, Bartholomew Agrawal, Anshika Tanrioven, Derin Luperchio, Teresa R Valencia, Angela M Jimenez Perestrelo, Tania Reddy, Karen Ha, Taekjip Philip, Jude M |
author_sort | Aifuwa, Ivie |
collection | PubMed |
description | The presence of senescent cells within tissues has been functionally linked to malignant transformations. Here, using tension-gauge tethers technology, particle-tracking microrheology, and quantitative microscopy, we demonstrate that senescent-associated secretory phenotype (SASP) derived from senescent fibroblasts impose nuclear lobulations and volume shrinkage on malignant cells, which stems from the loss of RhoA/ROCK/myosin II-based cortical tension. This loss in cytoskeletal tension induces decreased cellular contractility, adhesion, and increased mechanical compliance. These SASP-induced morphological changes are, in part, mediated by Lamin A/C. These findings suggest that SASP induces defective outside-in mechanotransduction from actomyosin fibers in the cytoplasm to the nuclear lamina, thereby triggering a cascade of biophysical and biomolecular changes in cells that associate with malignant transformations. |
format | Online Article Text |
id | pubmed-9830950 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-98309502023-01-26 Senescent stroma induces nuclear deformations in cancer cells via the inhibition of RhoA/ROCK/myosin II-based cytoskeletal tension Aifuwa, Ivie Kim, Byoung Choul Kamat, Pratik Starich, Bartholomew Agrawal, Anshika Tanrioven, Derin Luperchio, Teresa R Valencia, Angela M Jimenez Perestrelo, Tania Reddy, Karen Ha, Taekjip Philip, Jude M PNAS Nexus Research Report The presence of senescent cells within tissues has been functionally linked to malignant transformations. Here, using tension-gauge tethers technology, particle-tracking microrheology, and quantitative microscopy, we demonstrate that senescent-associated secretory phenotype (SASP) derived from senescent fibroblasts impose nuclear lobulations and volume shrinkage on malignant cells, which stems from the loss of RhoA/ROCK/myosin II-based cortical tension. This loss in cytoskeletal tension induces decreased cellular contractility, adhesion, and increased mechanical compliance. These SASP-induced morphological changes are, in part, mediated by Lamin A/C. These findings suggest that SASP induces defective outside-in mechanotransduction from actomyosin fibers in the cytoplasm to the nuclear lamina, thereby triggering a cascade of biophysical and biomolecular changes in cells that associate with malignant transformations. Oxford University Press 2022-12-06 /pmc/articles/PMC9830950/ /pubmed/36712940 http://dx.doi.org/10.1093/pnasnexus/pgac270 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the National Academy of Sciences. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Research Report Aifuwa, Ivie Kim, Byoung Choul Kamat, Pratik Starich, Bartholomew Agrawal, Anshika Tanrioven, Derin Luperchio, Teresa R Valencia, Angela M Jimenez Perestrelo, Tania Reddy, Karen Ha, Taekjip Philip, Jude M Senescent stroma induces nuclear deformations in cancer cells via the inhibition of RhoA/ROCK/myosin II-based cytoskeletal tension |
title | Senescent stroma induces nuclear deformations in cancer cells via the inhibition of RhoA/ROCK/myosin II-based cytoskeletal tension |
title_full | Senescent stroma induces nuclear deformations in cancer cells via the inhibition of RhoA/ROCK/myosin II-based cytoskeletal tension |
title_fullStr | Senescent stroma induces nuclear deformations in cancer cells via the inhibition of RhoA/ROCK/myosin II-based cytoskeletal tension |
title_full_unstemmed | Senescent stroma induces nuclear deformations in cancer cells via the inhibition of RhoA/ROCK/myosin II-based cytoskeletal tension |
title_short | Senescent stroma induces nuclear deformations in cancer cells via the inhibition of RhoA/ROCK/myosin II-based cytoskeletal tension |
title_sort | senescent stroma induces nuclear deformations in cancer cells via the inhibition of rhoa/rock/myosin ii-based cytoskeletal tension |
topic | Research Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9830950/ https://www.ncbi.nlm.nih.gov/pubmed/36712940 http://dx.doi.org/10.1093/pnasnexus/pgac270 |
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