How senescent tumor cell released mitochondrial DNA enhances tumor progression

Mitochondrial dysfunction is a feature of cellular senescence. 

The researchers find that senescent tumor cells release mitochondrial (mt)DNA into the extracellular space, where it is taken up by PMN-MDSCs.

Internalized mtDNA activates the cGAS-STING-NF-kB pathway, amplifying PMN-MDSC mediated tumor immunosuppression and contributing to tumor progression.

The authors show that STING activation directly induced NF-κB signaling, it also activated PKR-like endoplasmic reticulum kinase (PERK), which further amplified NF-κB activity, in PMN-MDSCs.

The researchers demonstrate that mtDNA release from senescent cells was mediated by voltage-dependent anion channels (VDACs), and inhibition of VDAC reduced extracellular mtDNA levels, reversed PMN-MDSC-driven immunosuppression, and enhanced chemotherapy efficacy in prostate cancer mouse models. 

https://www.cell.com/immunity/fulltext/S1074-7613(25)00124-4

https://sciencemission.com/Mitochondrial-DNA-released-by-senescent-tumor-cells