Unmasking senescence: context-dependent effects of SASP in cancer

Abstract

Cellular senescence plays a critical role in tumorigenesis. Once thought of as a tissue culture artefact by some researchers, senescence is now a major field of study. Although there are common molecular mechanisms that enforce the growth arrest that characterizes the phenotype, the impact of senescence is varied and can, in some instances, have opposite effects on tumorigenesis. It has become clearer that the cell of origin and the tissue in question dictate the impact of senescence on tumorigenesis. In this Review, we unravel this complexity by focusing on how senescence impacts tumorigenesis when it arises within incipient tumour cells versus stromal cells, and how these roles can change in different stages of disease progression. In addition, we highlight the diversity of the senescent phenotype and its functional output beyond growth arrest: the senescence-associated secretory phenotype (SASP). Fortunately, a number of new genetic and pharmacologic tools have been developed that are now allowing the senescence phenotype to be parsed further.