Senescence-messaging secretome: SMS-ing cellular stress

Abstract

Oncogene-induced cellular senescence constitutes a strong anti-proliferative response, which can be set in motion following either oncogene activation or loss of tumour suppressor signalling. It serves to limit the expansion of early neoplastic cells and as such is a potent cancer-protective response to oncogenic events. Recently emerging evidence points to a crucial role in oncogene-induced cellular senescence for the 'senescence-messaging secretome' or SMS, setting the stage for cross-talk between senescent cells and their environment. How are such signals integrated into a coordinated response and what are the implications of this unexpected finding?

Cytokine expression and signaling in drug-induced cellular senescence

“…IL6 and JAK1 are not essential for drug-induced DNA damage signaling and BDIS DNA damage signaling is a feature shared by all types of senescence (Campisi and d'Adda di Fagagna, 2007;Halazonetis et al, 2008), and given the recent reports on oncogene-induced and replicative senescence (Kuilman and Peeper, 2009), complemented by our present data on drug-induced senescence, cytokine/chemokine secretion may represent another universal aspect of cellular senescence. Given that downregulation of IL6 by RNA interference rescued cells from oncogene-induced senescence (Kuilman et al, 2008), we examined whether this causal relationship is also involved in BDIS.…”

“…This complex phenotype is characterized by persistent cell cycle arrest, morphological and functional features (Campisi, 2005), including profound changes in cell secretory phenotype (Kuilman and Peeper, 2009). Replicative senescence is primarily caused by telomeric DNA attrition, which can be accelerated, for example, by oxidative stress (von Zglinicki, 2002).…”

The adenoma hunt in colorectal cancer screening: defining the target

“…Overcoming senescence is therefore a crucial progression step in malignant transformation, during which stabilization of telomeres (mainly by activation of hTERT ), a defective DNA damage response (caused by mutations in genes such as ATM, and due to activity loss of the Rb and p53 pathway effectors) and interference with several signal transduction pathways (eg IL-6 signalling) play a role [20,22]. In addition, progression is marked by a substantial increase in the level of genomic instability, either as MSI or, more frequently, as CIN [23,24].…”

Les facteurs sécrétés associés à la sénescence

“…Ainsi, on sait maintenant que la sénescence, processus naturel au cours du vieillissement des cellules, peut aussi être induite dans des cellules tumorales. Quels que soient les stimulus, les gènes suppresseurs de tumeur p53 et Rb sont des protagonistes incontournables du processus de sénescence [1].Le double jeu de la sénescence sur le processus tumoral Un certain nombre d'études récentes ont montré que la sénescence inhibe le développement tumoral. En effet, qu'elle soit activée par des télomères défec-tueux, une stimulation oncogénique ou la réactivation d'un gène suppresseur de tumeur, la sénescence inhibe la formation tumorale et, dans certains cas, induit même une régression tumorale, principalement via l'activation des gènes suppresseurs p53 et Rb [1].…”

“…Quels que soient les stimulus, les gènes suppresseurs de tumeur p53 et Rb sont des protagonistes incontournables du processus de sénescence [1].…”