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Tissue fluidification promotes a cGAS–STING cytosolic DNA response in invasive breast cancer
The process in which locally confined epithelial malignancies progressively evolve into invasive cancers is often promoted by unjamming, a phase transition from a solid-like to a liquid-like state, which occurs in various tissues. Whether this tissue-level mechanical transition impacts phenotypes du...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10156599/ https://www.ncbi.nlm.nih.gov/pubmed/36581770 http://dx.doi.org/10.1038/s41563-022-01431-x |
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author | Frittoli, Emanuela Palamidessi, Andrea Iannelli, Fabio Zanardi, Federica Villa, Stefano Barzaghi, Leonardo Abdo, Hind Cancila, Valeria Beznoussenko, Galina V. Della Chiara, Giulia Pagani, Massimiliano Malinverno, Chiara Bhattacharya, Dipanjan Pisati, Federica Yu, Weimiao Galimberti, Viviana Bonizzi, Giuseppina Martini, Emanuele Mironov, Alexander A. Gioia, Ubaldo Ascione, Flora Li, Qingsen Havas, Kristina Magni, Serena Lavagnino, Zeno Pennacchio, Fabrizio Andrea Maiuri, Paolo Caponi, Silvia Mattarelli, Maurizio Martino, Sabata d’Adda di Fagagna, Fabrizio Rossi, Chiara Lucioni, Marco Tancredi, Richard Pedrazzoli, Paolo Vecchione, Andrea Petrini, Cristiano Ferrari, Francesco Lanzuolo, Chiara Bertalot, Giovanni Nader, Guilherme Foiani, Marco Piel, Matthieu Cerbino, Roberto Giavazzi, Fabio Tripodo, Claudio Scita, Giorgio |
author_facet | Frittoli, Emanuela Palamidessi, Andrea Iannelli, Fabio Zanardi, Federica Villa, Stefano Barzaghi, Leonardo Abdo, Hind Cancila, Valeria Beznoussenko, Galina V. Della Chiara, Giulia Pagani, Massimiliano Malinverno, Chiara Bhattacharya, Dipanjan Pisati, Federica Yu, Weimiao Galimberti, Viviana Bonizzi, Giuseppina Martini, Emanuele Mironov, Alexander A. Gioia, Ubaldo Ascione, Flora Li, Qingsen Havas, Kristina Magni, Serena Lavagnino, Zeno Pennacchio, Fabrizio Andrea Maiuri, Paolo Caponi, Silvia Mattarelli, Maurizio Martino, Sabata d’Adda di Fagagna, Fabrizio Rossi, Chiara Lucioni, Marco Tancredi, Richard Pedrazzoli, Paolo Vecchione, Andrea Petrini, Cristiano Ferrari, Francesco Lanzuolo, Chiara Bertalot, Giovanni Nader, Guilherme Foiani, Marco Piel, Matthieu Cerbino, Roberto Giavazzi, Fabio Tripodo, Claudio Scita, Giorgio |
author_sort | Frittoli, Emanuela |
collection | PubMed |
description | The process in which locally confined epithelial malignancies progressively evolve into invasive cancers is often promoted by unjamming, a phase transition from a solid-like to a liquid-like state, which occurs in various tissues. Whether this tissue-level mechanical transition impacts phenotypes during carcinoma progression remains unclear. Here we report that the large fluctuations in cell density that accompany unjamming result in repeated mechanical deformations of cells and nuclei. This triggers a cellular mechano-protective mechanism involving an increase in nuclear size and rigidity, heterochromatin redistribution and remodelling of the perinuclear actin architecture into actin rings. The chronic strains and stresses associated with unjamming together with the reduction of Lamin B1 levels eventually result in DNA damage and nuclear envelope ruptures, with the release of cytosolic DNA that activates a cGAS–STING (cyclic GMP-AMP synthase–signalling adaptor stimulator of interferon genes)-dependent cytosolic DNA response gene program. This mechanically driven transcriptional rewiring ultimately alters the cell state, with the emergence of malignant traits, including epithelial-to-mesenchymal plasticity phenotypes and chemoresistance in invasive breast carcinoma. |
format | Online Article Text |
id | pubmed-10156599 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-101565992023-05-05 Tissue fluidification promotes a cGAS–STING cytosolic DNA response in invasive breast cancer Frittoli, Emanuela Palamidessi, Andrea Iannelli, Fabio Zanardi, Federica Villa, Stefano Barzaghi, Leonardo Abdo, Hind Cancila, Valeria Beznoussenko, Galina V. Della Chiara, Giulia Pagani, Massimiliano Malinverno, Chiara Bhattacharya, Dipanjan Pisati, Federica Yu, Weimiao Galimberti, Viviana Bonizzi, Giuseppina Martini, Emanuele Mironov, Alexander A. Gioia, Ubaldo Ascione, Flora Li, Qingsen Havas, Kristina Magni, Serena Lavagnino, Zeno Pennacchio, Fabrizio Andrea Maiuri, Paolo Caponi, Silvia Mattarelli, Maurizio Martino, Sabata d’Adda di Fagagna, Fabrizio Rossi, Chiara Lucioni, Marco Tancredi, Richard Pedrazzoli, Paolo Vecchione, Andrea Petrini, Cristiano Ferrari, Francesco Lanzuolo, Chiara Bertalot, Giovanni Nader, Guilherme Foiani, Marco Piel, Matthieu Cerbino, Roberto Giavazzi, Fabio Tripodo, Claudio Scita, Giorgio Nat Mater Article The process in which locally confined epithelial malignancies progressively evolve into invasive cancers is often promoted by unjamming, a phase transition from a solid-like to a liquid-like state, which occurs in various tissues. Whether this tissue-level mechanical transition impacts phenotypes during carcinoma progression remains unclear. Here we report that the large fluctuations in cell density that accompany unjamming result in repeated mechanical deformations of cells and nuclei. This triggers a cellular mechano-protective mechanism involving an increase in nuclear size and rigidity, heterochromatin redistribution and remodelling of the perinuclear actin architecture into actin rings. The chronic strains and stresses associated with unjamming together with the reduction of Lamin B1 levels eventually result in DNA damage and nuclear envelope ruptures, with the release of cytosolic DNA that activates a cGAS–STING (cyclic GMP-AMP synthase–signalling adaptor stimulator of interferon genes)-dependent cytosolic DNA response gene program. This mechanically driven transcriptional rewiring ultimately alters the cell state, with the emergence of malignant traits, including epithelial-to-mesenchymal plasticity phenotypes and chemoresistance in invasive breast carcinoma. Nature Publishing Group UK 2022-12-29 2023 /pmc/articles/PMC10156599/ /pubmed/36581770 http://dx.doi.org/10.1038/s41563-022-01431-x Text en © The Author(s) 2022, corrected publication 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Frittoli, Emanuela Palamidessi, Andrea Iannelli, Fabio Zanardi, Federica Villa, Stefano Barzaghi, Leonardo Abdo, Hind Cancila, Valeria Beznoussenko, Galina V. Della Chiara, Giulia Pagani, Massimiliano Malinverno, Chiara Bhattacharya, Dipanjan Pisati, Federica Yu, Weimiao Galimberti, Viviana Bonizzi, Giuseppina Martini, Emanuele Mironov, Alexander A. Gioia, Ubaldo Ascione, Flora Li, Qingsen Havas, Kristina Magni, Serena Lavagnino, Zeno Pennacchio, Fabrizio Andrea Maiuri, Paolo Caponi, Silvia Mattarelli, Maurizio Martino, Sabata d’Adda di Fagagna, Fabrizio Rossi, Chiara Lucioni, Marco Tancredi, Richard Pedrazzoli, Paolo Vecchione, Andrea Petrini, Cristiano Ferrari, Francesco Lanzuolo, Chiara Bertalot, Giovanni Nader, Guilherme Foiani, Marco Piel, Matthieu Cerbino, Roberto Giavazzi, Fabio Tripodo, Claudio Scita, Giorgio Tissue fluidification promotes a cGAS–STING cytosolic DNA response in invasive breast cancer |
title | Tissue fluidification promotes a cGAS–STING cytosolic DNA response in invasive breast cancer |
title_full | Tissue fluidification promotes a cGAS–STING cytosolic DNA response in invasive breast cancer |
title_fullStr | Tissue fluidification promotes a cGAS–STING cytosolic DNA response in invasive breast cancer |
title_full_unstemmed | Tissue fluidification promotes a cGAS–STING cytosolic DNA response in invasive breast cancer |
title_short | Tissue fluidification promotes a cGAS–STING cytosolic DNA response in invasive breast cancer |
title_sort | tissue fluidification promotes a cgas–sting cytosolic dna response in invasive breast cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10156599/ https://www.ncbi.nlm.nih.gov/pubmed/36581770 http://dx.doi.org/10.1038/s41563-022-01431-x |
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