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

Autor: Frittoli E; IFOM, the FIRC Institute of Molecular Oncology, Milan, Italy., Palamidessi A; IFOM, the FIRC Institute of Molecular Oncology, Milan, Italy. andrea.palamidessi@ifom.eu., Iannelli F; IFOM, the FIRC Institute of Molecular Oncology, Milan, Italy., Zanardi F; IFOM, the FIRC Institute of Molecular Oncology, Milan, Italy., Villa S; Department of Medical Biotechnology and Translational Medicine, University of Milan, Segrate, Italy.; Max Plank Institute for Dynamics and Self-Organization, Göttingen, Germany., Barzaghi L; IFOM, the FIRC Institute of Molecular Oncology, Milan, Italy., Abdo H; IFOM, the FIRC Institute of Molecular Oncology, Milan, Italy., Cancila V; Department of Health Sciences, Human Pathology Section, University of Palermo School of Medicine, Palermo, Italy., Beznoussenko GV; IFOM, the FIRC Institute of Molecular Oncology, Milan, Italy., Della Chiara G; IFOM, the FIRC Institute of Molecular Oncology, Milan, Italy., Pagani M; IFOM, the FIRC Institute of Molecular Oncology, Milan, Italy.; Department of Medical Biotechnology and Translational Medicine, University of Milan, Segrate, Italy., Malinverno C; IFOM, the FIRC Institute of Molecular Oncology, Milan, Italy., Bhattacharya D; IFOM, the FIRC Institute of Molecular Oncology, Milan, Italy., Pisati F; IFOM, the FIRC Institute of Molecular Oncology, Milan, Italy., Yu W; Institute of Molecular and Cell Biology, A*STAR, Singapore, & Bioinformatics Institute, A*STAR, Singapore, Singapore., Galimberti V; European Institute of Oncology (IEO) IRCCS, Milan, Italy., Bonizzi G; European Institute of Oncology (IEO) IRCCS, Milan, Italy., Martini E; IFOM, the FIRC Institute of Molecular Oncology, Milan, Italy., Mironov AA; IFOM, the FIRC Institute of Molecular Oncology, Milan, Italy., Gioia U; IFOM, the FIRC Institute of Molecular Oncology, Milan, Italy., Ascione F; IFOM, the FIRC Institute of Molecular Oncology, Milan, Italy., Li Q; IFOM, the FIRC Institute of Molecular Oncology, Milan, Italy., Havas K; IFOM, the FIRC Institute of Molecular Oncology, Milan, Italy., Magni S; IFOM, the FIRC Institute of Molecular Oncology, Milan, Italy., Lavagnino Z; IFOM, the FIRC Institute of Molecular Oncology, Milan, Italy., Pennacchio FA; IFOM, the FIRC Institute of Molecular Oncology, Milan, Italy., Maiuri P; IFOM, the FIRC Institute of Molecular Oncology, Milan, Italy.; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Naples, Italy., Caponi S; Istituto Officina dei Materiali, National Research Council (IOM-CNR), Unit of Perugia, c/o Department of Physics and Geology, University of Perugia, Perugia, Italy., Mattarelli M; Department of Physics and Geology, University of Perugia, Perugia, Italy., Martino S; Department of Chemistry, Biology and Biotechnology, Biochemical and Biotechnological Sciences, University of Perugia, Perugia, Italy., d'Adda di Fagagna F; IFOM, the FIRC Institute of Molecular Oncology, Milan, Italy.; Institute of Molecular Genetics, National Research Council, Pavia, Italy., Rossi C; Unit of Anatomic Pathology, Department of Molecular Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy., Lucioni M; Unit of Anatomic Pathology, Department of Molecular Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy., Tancredi R; Medical Oncology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.; S.C. Oncologia Medica, ASST Melegnano e della Martesana, Ospedale Uboldo, Cernusco sul Naviglio, Milan, Italy., Pedrazzoli P; Medical Oncology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.; Department of Internal Medicine and Medical Therapy, University of Pavia, Pavia, Italy., Vecchione A; Department of Clinical and Molecular Medicine, University of Roma, La Sapienza, Rome, Italy., Petrini C; IFOM, the FIRC Institute of Molecular Oncology, Milan, Italy., Ferrari F; IFOM, the FIRC Institute of Molecular Oncology, Milan, Italy.; Institute of Molecular Genetics, National Research Council, Pavia, Italy., Lanzuolo C; Institute of Biomedical Technologies, National Research Council, Milan, Italy.; National Institute of Molecular Genetics Romeo and Enrica Invernizzi, INGM, Milan, Italy., Bertalot G; Department of Pathology, S. Chiara Hospital, Azienda Provinciale per i Servizi Sanitari, Trento, Italy.; CISMed University of Trento, University of Trento, Trento, Italy., Nader G; Institut Curie and Institut Pierre Gilles de Gennes, PSL Research University, CNRS, UMR-144, Paris, France.; 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., Foiani M; IFOM, the FIRC Institute of Molecular Oncology, Milan, Italy.; Department of Oncology and Haemato-Oncology, University of Milan, Milan, Italy., Piel M; Institut Curie and Institut Pierre Gilles de Gennes, PSL Research University, CNRS, UMR-144, Paris, France., Cerbino R; Department of Medical Biotechnology and Translational Medicine, University of Milan, Segrate, Italy.; Faculty of Physics, University of Vienna, Vienna, Austria., Giavazzi F; Department of Medical Biotechnology and Translational Medicine, University of Milan, Segrate, Italy. fabio.giavazzi@unimi.it., Tripodo C; IFOM, the FIRC Institute of Molecular Oncology, Milan, Italy. claudio.tripodo@unipa.it.; Department of Health Sciences, Human Pathology Section, University of Palermo School of Medicine, Palermo, Italy. claudio.tripodo@unipa.it., Scita G; IFOM, the FIRC Institute of Molecular Oncology, Milan, Italy. giorgio.scita@ifom.eu.; Department of Oncology and Haemato-Oncology, University of Milan, Milan, Italy. giorgio.scita@ifom.eu.
Jazyk: angličtina
Zdroj: Nature materials [Nat Mater] 2023 May; Vol. 22 (5), pp. 644-655. Date of Electronic Publication: 2022 Dec 29.
DOI: 10.1038/s41563-022-01431-x
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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