Mechano-metabolic feedback connects tissue fluidity to mitochondrial DNA-dependent immunity in breast cancer - PubMed
2 hours ago
- #Immunotherapy
- #Breast Cancer
- #Mitochondrial Dynamics
- Mechano-metabolic feedback links tissue fluidity to mitochondrial DNA-dependent immunity in breast cancer.
- Elevated RAB5A-driven endocytosis causes tissue fluidization during breast cancer invasion.
- RAB5A disrupts the AMPK-AKAP1-DRP1 pathway, leading to mitochondrial elongation and outer membrane permeabilization via BAX/BAK pores.
- Palmitoylated GASDERMIN A oligomerization amplifies mitochondrial damage, releasing mitochondrial DNA that activates the cGAS-STING innate immune pathway.
- RAB5A-expressing tumors show slower growth, increased immune infiltration, and enhanced sensitivity to immune-checkpoint blockade, dependent on BAX/BAK, cGAS/STING, and mtDNA.
- Findings connect mechanical stress, mitochondrial dynamics, and innate immunity, offering strategies to improve immunotherapy response.