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| Status |
Public on Sep 27, 2022 |
| Title |
Tissue fluidification promotes a cGAS/STING-mediated cytosolic DNA response in invasive breast cancer [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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 that occurs in various tissues. Whether this tissue-level mechanical transition impact phenotypes during carcinoma progression remains unclear. We show, here that the large fluctuations in cell density that accompany unjamming result in repeated mechanical deformations of cells and nuclei. Cells react to these protracted mechanical stresses by mounting a mechano-protective response that includes enlarged nuclear size and rigidity, altered heterochromatin distribution, and the remodeling 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-dependent cytosolic DNA response gene program. This mechanically-driven transcriptional rewiring ultimately results in a change in cell state, with the emergence of malignant traits, including epithelial-to-mesenchymal plasticity phenotypes and chemo-resistance in invasive breast carcinoma.
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| Overall design |
RNA-seq, 3 replicates per condition, 2 conditions (CTR, RAB5A), 2 cell lines
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| Contributor(s) |
Frittoli E, Palamidessi A, Iannelli F, Zanardi F, Villa S, Barzaghi L, Abdo H, Cancila V, Beznuskenko G, Chiara Gd, Pagani M, Malinverno C, Bhattacharya D, Pisati F, Yu W, Galimberti V, Bonizzi G, Martini E, Mironov A, Gioia U, d’Adda di Fagagna F, Rossi C, Lucioni M, Tancredi R, Pedrazzoli P, Vecchione A, Petrini C, Ferrari F, Lanzuolo C, Nader G, Foiani M, Piel M, Cerbino R, Giavazzi F, Tripodo C, Scita G |
| Citation(s) |
36581770 |
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| Submission date |
Sep 05, 2021 |
| Last update date |
Aug 02, 2023 |
| Contact name |
Giorgio Scita |
| E-mail(s) |
giorgio.scita@ifom.eu
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| Organization name |
IFOM, The AIRC Institute of Molecular Oncology
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| Street address |
via Adamello, 16
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| City |
Milan |
| State/province |
Mi |
| ZIP/Postal code |
20139 |
| Country |
Italy |
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| Platforms (1) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA760933 |
| SRA |
SRP335751 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE183479_RAW.tar |
1.3 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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