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Series GSE183539 Query DataSets for GSE183539
Status Public on Sep 27, 2022
Title Tissue fluidification promotes a cGAS/STING-mediated cytosolic DNA response in invasive breast cancer [SAMMY-seq]
Organism Homo sapiens
Experiment type Other
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.
 
Overall design SAMMY-seq analysis was performed in three biological replicates for of control and RAB5 overexpression samples in MCF10DCIS.com cells.
 
Contributor(s) Lanzuolo C, Petrini C, Ferrari F, Palamedessi A, Frittoli E, Scita G
Citation(s) 36581770
Submission date Sep 06, 2021
Last update date Aug 02, 2023
Contact name Giorgio Scita
E-mail(s) giorgio.scita@ifom.eu
Organization name IFOM, The AIRC Institute of Molecular Oncology
Street address via Adamello, 16
City Milan
State/province Mi
ZIP/Postal code 20139
Country Italy
 
Platforms (1)
GPL21697 NextSeq 550 (Homo sapiens)
Samples (18)
GSM5560073 Control Replicate 1 SAMMY-seq fraction S2
GSM5560074 Control Replicate 1 SAMMY-seq fraction S3
GSM5560075 Control Replicate 1 SAMMY-seq fraction S4
Relations
BioProject PRJNA761201
SRA SRP335918

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Supplementary file Size Download File type/resource
GSE183539_RAW.tar 6.2 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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