Cellular senescence and tumor promotion

Abstract

Cellular senescence is a state of irreversible growth arrest activated by a complex response to stress signals that lead to DNA or mitochondrial damages. Thus, cellular senescence derives from stress-activated programs, as opposed to other cellular states of irreversible growth arrest, such as post-mitosis and terminal differentiation, which are a consequence of developmental-activated programs. Senescent cells are characterized by the expression of different nonexclusive markers with various functions, and most senescent cells secrete a suite of cytokines, growth factors, and proteases, known as the senescence-associated secretory phenotype (SASP). The senescence growth arrest represents a potent barrier to prevent the propagation of damaged cells and to maintain tissue homeostasis. Moreover, the senescence program is a well-established tumor suppressive mechanism, and different anticancer therapeutic strategies are aimed to induce cancer cells to senesce. However, an excessive accumulation of senescent cells and their secretory phenotype can drive different pathologies associated with age, including cancer. Thus, cellular senescence can begin as a potent tumor suppressive mechanism and end with a tumor-promoting passing through positive modulation of tissue repair. For this reason, interventions aimed at interfering with the deleterious functions of senescent cells are under development.