New mechanism involved in senescence modulates in
Cellular senescence is a natural tumor suppression mechanism that stably halts proliferation of damaged or premalignant cells. Senescent cells also represent a trigger of inflammation and immune reaction as they produce an array of inflammatory molecules collectively known as senescence-associated secretory phenotype (SASP).
"Uncovering an important step that mediates the senescence response and enables the SASP, we identified a novel molecular pathway involved in immunotherapy response," said lead researcher Rugang Zhang, Ph.D., deputy director of The Wistar Institute Cancer Center, professor and co-program leader of the Gene Expression and Regulation Program. "We suggest that this pathway might be targeted to modulate senescence-inducing effects of cancer therapeutics and affect response of senescent cancer cells to immunotherapy."
Cells that have been exposed to various stressors and have suffered substantial DNA damage, for example during chemotherapy, transport pieces of DNA from the nucleus to the cytoplasm as a way to signal that something is wrong. The cGMP-AMP synthase (cGAS) senses cytosolic DNA and activates senescence and immunity by triggering a cascade of cellular events that culminate with production of the SASP. How cGAS senses DNA was unknown.标签：