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      Tissue fluidification promotes a cGAS–STING cytosolic DNA response in invasive breast cancer

      research-article
      1 , 1 , , 1 , 1 , 2 , 21 , 1 , 1 , 3 , 1 , 1 , 1 , 2 , 1 , 1 , 1 , 4 , 5 , 5 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 22 , 6 , 7 , 8 , 1 , 9 , 10 , 10 , 11 , 23 , 11 , 12 , 13 , 1 , 1 , 9 , 14 , 15 , 16 , 17 , 18 , 24 , 1 , 19 , 18 , 2 , 20 , 2 , , 1 , 3 , , 1 , 19 ,
      Nature Materials
      Nature Publishing Group UK
      Cellular motility, Biomaterials - cells, Cancer

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          Abstract

          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.

          Abstract

          Tissue fluidification in invasive breast carcinoma is accompanied by mechanical stresses that compromise nuclear integrity and liberate DNA, resulting in the activation of a pro-inflammatory response that shape tumour evolution and progression.

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          Fiji: an open-source platform for biological-image analysis.

          Fiji is a distribution of the popular open-source software ImageJ focused on biological-image analysis. Fiji uses modern software engineering practices to combine powerful software libraries with a broad range of scripting languages to enable rapid prototyping of image-processing algorithms. Fiji facilitates the transformation of new algorithms into ImageJ plugins that can be shared with end users through an integrated update system. We propose Fiji as a platform for productive collaboration between computer science and biology research communities.
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            • Record: found
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            NIH Image to ImageJ: 25 years of image analysis

            For the past twenty five years the NIH family of imaging software, NIH Image and ImageJ have been pioneers as open tools for scientific image analysis. We discuss the origins, challenges and solutions of these two programs, and how their history can serve to advise and inform other software projects.
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              Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway.

              The presence of DNA in the cytoplasm of mammalian cells is a danger signal that triggers host immune responses such as the production of type I interferons. Cytosolic DNA induces interferons through the production of cyclic guanosine monophosphate-adenosine monophosphate (cyclic GMP-AMP, or cGAMP), which binds to and activates the adaptor protein STING. Through biochemical fractionation and quantitative mass spectrometry, we identified a cGAMP synthase (cGAS), which belongs to the nucleotidyltransferase family. Overexpression of cGAS activated the transcription factor IRF3 and induced interferon-β in a STING-dependent manner. Knockdown of cGAS inhibited IRF3 activation and interferon-β induction by DNA transfection or DNA virus infection. cGAS bound to DNA in the cytoplasm and catalyzed cGAMP synthesis. These results indicate that cGAS is a cytosolic DNA sensor that induces interferons by producing the second messenger cGAMP.
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                Author and article information

                Contributors
                andrea.palamidessi@ifom.eu
                fabio.giavazzi@unimi.it
                claudio.tripodo@unipa.it
                giorgio.scita@ifom.eu
                Journal
                Nat Mater
                Nat Mater
                Nature Materials
                Nature Publishing Group UK (London )
                1476-1122
                1476-4660
                29 December 2022
                29 December 2022
                2023
                : 22
                : 5
                : 644-655
                Affiliations
                [1 ]GRID grid.7678.e, ISNI 0000 0004 1757 7797, IFOM, the FIRC Institute of Molecular Oncology, ; Milan, Italy
                [2 ]GRID grid.4708.b, ISNI 0000 0004 1757 2822, Department of Medical Biotechnology and Translational Medicine, , University of Milan, ; Segrate, Italy
                [3 ]GRID grid.10776.37, ISNI 0000 0004 1762 5517, Department of Health Sciences, Human Pathology Section, , University of Palermo School of Medicine, ; Palermo, Italy
                [4 ]GRID grid.418812.6, ISNI 0000 0004 0620 9243, Institute of Molecular and Cell Biology, A*STAR, Singapore, & Bioinformatics Institute, A*STAR, ; Singapore, Singapore
                [5 ]GRID grid.15667.33, ISNI 0000 0004 1757 0843, European Institute of Oncology (IEO) IRCCS, ; Milan, Italy
                [6 ]GRID grid.9027.c, ISNI 0000 0004 1757 3630, Istituto Officina dei Materiali, National Research Council (IOM-CNR), Unit of Perugia, c/o Department of Physics and Geology, , University of Perugia, ; Perugia, Italy
                [7 ]GRID grid.9027.c, ISNI 0000 0004 1757 3630, Department of Physics and Geology, , University of Perugia, ; Perugia, Italy
                [8 ]GRID grid.9027.c, ISNI 0000 0004 1757 3630, Department of Chemistry, Biology and Biotechnology, Biochemical and Biotechnological Sciences, , University of Perugia, ; Perugia, Italy
                [9 ]GRID grid.5326.2, ISNI 0000 0001 1940 4177, Institute of Molecular Genetics, National Research Council, ; Pavia, Italy
                [10 ]GRID grid.8982.b, ISNI 0000 0004 1762 5736, Unit of Anatomic Pathology, Department of Molecular Medicine, Fondazione IRCCS Policlinico San Matteo, , University of Pavia, ; Pavia, Italy
                [11 ]GRID grid.419425.f, ISNI 0000 0004 1760 3027, Medical Oncology Unit, Fondazione IRCCS Policlinico San Matteo, ; Pavia, Italy
                [12 ]GRID grid.8982.b, ISNI 0000 0004 1762 5736, Department of Internal Medicine and Medical Therapy, , University of Pavia, ; Pavia, Italy
                [13 ]GRID grid.7841.a, Department of Clinical and Molecular Medicine, , University of Roma, La Sapienza, ; Rome, Italy
                [14 ]GRID grid.5326.2, ISNI 0000 0001 1940 4177, Institute of Biomedical Technologies, , National Research Council, ; Milan, Italy
                [15 ]GRID grid.428717.f, ISNI 0000 0004 1802 9805, National Institute of Molecular Genetics Romeo and Enrica Invernizzi, , INGM, ; Milan, Italy
                [16 ]GRID grid.415176.0, ISNI 0000 0004 1763 6494, Department of Pathology, , S. Chiara Hospital, Azienda Provinciale per i Servizi Sanitari, ; Trento, Italy
                [17 ]GRID grid.11696.39, ISNI 0000 0004 1937 0351, CISMed University of Trento, , University of Trento, ; Trento, Italy
                [18 ]GRID grid.4444.0, ISNI 0000 0001 2112 9282, Institut Curie and Institut Pierre Gilles de Gennes, , PSL Research University, CNRS, UMR-144, ; Paris, France
                [19 ]GRID grid.4708.b, ISNI 0000 0004 1757 2822, Department of Oncology and Haemato-Oncology, , University of Milan, ; Milan, Italy
                [20 ]GRID grid.10420.37, ISNI 0000 0001 2286 1424, Faculty of Physics, , University of Vienna, ; Vienna, Austria
                [21 ]Present Address: Max Plank Institute for Dynamics and Self-Organization, Göttingen, Germany
                [22 ]GRID grid.4691.a, ISNI 0000 0001 0790 385X, Present Address: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, , Università degli Studi di Napoli Federico II, ; Naples, Italy
                [23 ]GRID grid.476841.8, Present Address: S.C. Oncologia Medica, ASST Melegnano e della Martesana, Ospedale Uboldo, Cernusco sul Naviglio, ; Milan, Italy
                [24 ]GRID grid.25879.31, ISNI 0000 0004 1936 8972, Present Address: Cell Pathology Children’s Hospital of Philadelphia, Research Institute Department of Pathology and Laboratory Medicine University of Pennsylvania Perelman School of Medicine, ; Philadelphia, PA USA
                Author information
                http://orcid.org/0000-0002-7134-7023
                http://orcid.org/0000-0002-2777-1417
                http://orcid.org/0000-0002-3174-6441
                http://orcid.org/0000-0002-1876-4098
                http://orcid.org/0000-0001-5211-3814
                http://orcid.org/0000-0002-6409-4291
                http://orcid.org/0000-0001-5092-1009
                http://orcid.org/0000-0002-3375-7726
                http://orcid.org/0000-0003-4730-9710
                http://orcid.org/0000-0001-5079-445X
                http://orcid.org/0000-0002-4219-3256
                http://orcid.org/0000-0001-9184-7968
                http://orcid.org/0000-0002-9253-1671
                http://orcid.org/0000-0002-9419-7160
                http://orcid.org/0000-0002-5497-6856
                http://orcid.org/0000-0002-2848-177X
                http://orcid.org/0000-0003-0434-7741
                http://orcid.org/0000-0003-4930-0592
                http://orcid.org/0000-0002-0821-6231
                http://orcid.org/0000-0001-7984-1889
                Article
                1431
                10.1038/s41563-022-01431-x
                10156599
                36581770
                57a3624a-8f9e-4167-a1fd-712d621b9681
                © The Author(s) 2022, corrected publication 2023

                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/.

                History
                : 25 August 2021
                : 2 November 2022
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100005010, Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research);
                Award ID: IG#18621
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100003407, Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research);
                Award ID: PRIN 2017, 2017HWTP2K
                Award Recipient :
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                © Springer Nature Limited 2023

                Materials science
                cellular motility,biomaterials - cells,cancer
                Materials science
                cellular motility, biomaterials - cells, cancer

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