2015 Volume 15 Issue 1 Pages 9-19
Cellular senescence is known to be the state of permanent cell cycle arrest. It is induced by a variety of potentially oncogenic stimuli and has therefore long been believed to suppress tumorigenesis, acting as a guardian of tissue homeostasis. However, recent evidences revealed that senescent cells also promote the secretion of inflammatory cytokines, chemokines, growth factors and matrix remodelling factors. These factors can alter the local tissue environment and contribute to some beneficial effects, such as tissue repair, but also to deleterious effects, such as chronic inflammation and cancer development, depending on the biological context. This newly identified senescence phenotype, termed the senescence-associated secretory phenotype (SASP), can be induced by DNA damage that promotes the senescence cell cycle arrest. These senescence-associated secreted factors are involved in homeostatic disorders, such as cancer. Our recent study focused on obesity-associated pathological conditions, and particularly on the link between obesity and liver cancer. We found that the obesity-induced gut microbial metabolite triggered the senescence and SASP of hepatic stellate cells through enterohepatic circulation that contribute to the formation of tumor-promoting microenvironments. These results suggest the role of the senescence-associated secretome in cancer-associated microenvironments in obesity-associated liver cancer.
