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

Frittoli, E., Palamidessi, A., Iannelli, F., Zanardi, F., Villa, S., Barzaghi, L., et al. (2023). Tissue fluidification promotes a cGAS–STING cytosolic DNA response in invasive breast cancer. Nature Materials, 22, 644-655. doi:10.1038/s41563-022-01431-x.

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Item Permalink: https://hdl.handle.net/21.11116/0000-000C-A828-A Version Permalink: https://hdl.handle.net/21.11116/0000-000D-13F5-9
Genre: Journal Article

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 Creators:
Frittoli, Emanuela, Author
Palamidessi, Andrea, Author
Iannelli, Fabio, Author
Zanardi, Federica, Author
Villa, Stefano1, Author           
Barzaghi, Leonardo, Author
Abdo, Hind, Author
Cancila, Valeria, Author
Beznoussenko, Galina V., Author
Chiara, Giulia Della, Author
Pagani, Massimiliano, Author
Malinverno, Chiara, Author
Bhattacharya, Dipanjan, Author
Pisati, Federica, Author
Yu, Weimiao, Author
Galimberti, Viviana, Author
Bonizzi, Giuseppina, Author
Martini, Emanuele, Author
Mironov, Alexander A., Author
Gioia, Ubaldo, Author
Ascione, Flora, AuthorLi, Qingsen, AuthorHavas, Kristina, AuthorMagni, Serena, AuthorLavagnino, Zeno, AuthorPennacchio, Fabrizio Andrea, AuthorMaiuri, Paolo, AuthorCaponi, Silvia, AuthorMattarelli, Maurizio, AuthorMartino, Sabata, AuthorFagagna, Fabrizio d’Adda di, AuthorRossi, Chiara, AuthorLucioni, Marco, AuthorTancredi, Richard, AuthorPedrazzoli, Paolo, AuthorVecchione, Andrea, AuthorPetrini, Cristiano, AuthorFerrari, Francesco, AuthorLanzuolo, Chiara, AuthorBertalot, Giovanni, AuthorNader, Guilherme, AuthorFoiani, Marco, AuthorPiel, Matthieu, AuthorCerbino, Roberto, AuthorGiavazzi, Fabio, AuthorTripodo, Claudio, AuthorScita, Giorgio, Author more..
Affiliations:
1Laboratory for Fluid Physics, Pattern Formation and Biocomplexity, Max Planck Institute for Dynamics and Self-Organization, Max Planck Society, ou_2063287              

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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.

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Language(s): eng - English
 Dates: 2022-12-292023-05
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1038/s41563-022-01431-x
 Degree: -

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Project name : We thank M. Riboni, S. Minardi, V. Dall’Olio and L. Tizzoni at Cogentech for gene expression profiling and qRT-PCR services; D. Parazzoli, S. Barozzi and the imaging unit of IFOM cell culture facility for technical assistance; F. Pramotton, A. Poli and the cleanroom facilities of the Binning and Rohrer Nanotechnology Center for assistance with the microchannel apparatus. Thank you to the Biobankl for Translational and Digital Medicine Unit (B4MED) of the European Institute of Oncology for support in providing breast cancer samples. This work was supported by ERC-Synergy (101071470-SHAPINCELLFATE) to G.S.; Associazione Italiana per la Ricerca sul Cancro (AIRC IG#18621 and 5Xmille#22759 to G.S., M.F. and C.T.; AIRC-IG-#21416 to M.F.; MyFirstAIRCgrant MFAG#22083 to F.G. and S.V.; AIRC-IG #21762 and AIRC 5×1000#21091 to F.d.F); the Italian Ministry of University and Scientific Research (PRIN 2017, 2017HWTP2K to G.S.; PRIN-2015SJLMB9 to M.F. and F.d.F.); the European Research Council (ERC advanced grant#835103 to F.d.F.); Progetto AriSLA 2021 ‘DDR & ALS; FRRB—Fondazione Regionale per la Ricerca Biomedica—under the frame of EJP RD, the European Joint Programme on Rare Diseases with funding from the European Union’s Horizon 2020 research and innovation programme under the EJP RD COFUND-EJP N° 825575 to F.g.F.; from LABEX DCBIOL (ANR-10-IDEX-0001-02 PSL* and ANR-11-LABX-0043), ANR ANR-17-CE15-0025-01 and ANR-18-CE92-0022-01, INSERM 19CS007-00, INCA PLBIO to N.M.; and INCA PLBIO 2019-1-PL BIO-07-ICR-1, INSERM Plan Cancer Single Cell grant 19CS007-00 to M.P.. H.A. is supported by a fellowship from Fondazione Umberto Veronesi; L.B. is supported by a fellowship from the Associazione Italiana per la Ricerca sul Cancro.
Grant ID : -
Funding program : -
Funding organization : -
Project name : TeloRNAging
Grant ID : 835103
Funding program : Horizon 2020 (H2020)
Funding organization : European Commission (EC)
Project name : EJP RD
Grant ID : 825575
Funding program : Horizon 2020 (H2020)
Funding organization : European Commission (EC)

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Title: Nature Materials
  Abbreviation : Nat. Mater.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: London, UK : Nature Pub. Group
Pages: - Volume / Issue: 22 Sequence Number: - Start / End Page: 644 - 655 Identifier: ISSN: 1476-1122
CoNE: https://pure.mpg.de/cone/journals/resource/111054835734000