Stress-induced Cellular Senescence Contributes to Chronic Inflammation and Cancer Progression

Abstract

Cellular senescence has long been considered to act as a tumor suppressor or tumor suppression mechanism and described as a phenomenon of irreversible cell cycle arrest. Cellular senescence, however, is now considered to have physiological functions other than tumor suppression; it has been found to be involved in embryogenesis, tissue/organ aging, and wound healing. Surprisingly, cellular senescence is also demonstrated to have a tumor progressive role in certain situations. Senescent cells exhibit secretory phenotypes called senescence-associated secretory phenotype (SASP), which secrete a variety of SASP factors including inflammatory cytokines, chemokines, and growth factors, as well as matrix remodeling factors that promote the alteration of neighboring tissue microenvironments. Such SASP factors have been known to drive the mechanisms underlying the pleiotropic features of cellular senescence. In this review, we examine current knowledge of cellular senescence at molecular and cellular levels, with a focus on chronic inflammation and tumor progression.