| First Author | Lau L | Year | 2019 |
| Journal | Mol Cell Biol | Volume | 39 |
| Issue | 12 | PubMed ID | 30988157 |
| Mgi Jnum | J:291345 | Mgi Id | MGI:6446611 |
| Doi | 10.1128/MCB.00586-18 | Citation | Lau L, et al. (2019) Uncoupling the Senescence-Associated Secretory Phenotype from Cell Cycle Exit via Interleukin-1 Inactivation Unveils Its Protumorigenic Role. Mol Cell Biol 39(12) |
| abstractText | Cellular senescence has emerged as a potent tumor suppressor mechanism in numerous human neoplasias. Senescent cells secrete a distinct set of factors, collectively termed the senescence-associated secretory phenotype (SASP), which has been postulated to carry both pro- and antitumorigenic properties depending on tissue context. However, the in vivo effect of the SASP is poorly understood due to the difficulty of studying the SASP independently of other senescence-associated phenotypes. Here, we report that disruption of the interleukin-1 (IL-1) pathway completely uncouples the SASP from other senescence-associated phenotypes such as cell cycle exit. Transcriptome profiling of IL-1 receptor (IL-1R)-depleted senescent cells indicates that IL-1 controls the late arm of the senescence secretome, which consists of proinflammatory cytokines induced by NF-kappaB. Our data suggest that both IL-1alpha and IL-1beta signal through IL-1R to upregulate the SASP in a cooperative manner. Finally, we show that IL-1alpha inactivation impairs tumor progression and immune cell infiltration without affecting cell cycle arrest in a mouse model of pancreatic cancer, highlighting the protumorigenic property of the IL-1-dependent SASP in this context. These findings provide novel insight into the therapeutic potential of targeting the IL-1 pathway in inflammatory cancers. |
