Search results for "TREX1"

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Compromised nuclear envelope integrity drives TREX1-dependent DNA damage and tumor cell invasion

2021

Although mutations leading to a compromised nuclear envelope cause diseases such as muscular dystrophies or accelerated aging, the consequences of mechanically induced nuclear envelope ruptures are less known. Here, we show that nuclear envelope ruptures induce DNA damage that promotes senescence in non-transformed cells and induces an invasive phenotype in human breast cancer cells. We find that the endoplasmic reticulum (ER)-associated exonuclease TREX1 translocates into the nucleus after nuclear envelope rupture and is required to induce DNA damage. Inside the mammary duct, cellular crowding leads to nuclear envelope ruptures that generate TREX1-dependent DNA damage, thereby driving the …

SenescenceExonucleaseDNA damageNuclear Envelope[SDV]Life Sciences [q-bio]Breast NeoplasmsBiologySettore MED/08 - Anatomia PatologicaGeneral Biochemistry Genetics and Molecular BiologyCell LineMicemedicineSettore MED/05 - Patologia ClinicaAnimalsHumansNeoplasm InvasivenessEpithelial–mesenchymal transitionCellular SenescenceEndoplasmic reticulumPhosphoproteinsXenograft Model Antitumor AssaysCell biology[SDV] Life Sciences [q-bio]medicine.anatomical_structureExodeoxyribonucleasesCancer cellProteolysisbiology.proteinTREX1 nuclear envelope rupture DNA damage mammary duct carcinoma tumor invasion senescence breast cancer cGAS confinement epithelial to mesenchymal transition Animals Breast Neoplasms Cell Line Cellular Senescence Collagen Disease Progression Exodeoxyribonucleases Female Humans Mice Neoplasm InvasivenessNuclear Envelope PhosphoproteinsProteolysis Xenograft Model Antitumor Assays DNA DamageDisease ProgressionFemaleCollagenNucleusExtracellular Matrix DegradationDNA Damage
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