| First Author | Hari P | Year | 2019 |
| Journal | Sci Adv | Volume | 5 |
| Issue | 6 | Pages | eaaw0254 |
| PubMed ID | 31183403 | Mgi Jnum | J:288756 |
| Mgi Id | MGI:6430051 | Doi | 10.1126/sciadv.aaw0254 |
| Citation | Hari P, et al. (2019) The innate immune sensor Toll-like receptor 2 controls the senescence-associated secretory phenotype. Sci Adv 5(6):eaaw0254 |
| abstractText | Cellular senescence is a stress response program characterized by a robust cell cycle arrest and the induction of a proinflammatory senescence-associated secretory phenotype (SASP) that is triggered through an unknown mechanism. Here, we show that, during oncogene-induced senescence (OIS), the Toll-like receptor 2 (TLR2) and its partner TLR10 are key mediators of senescence in vitro and in murine models. TLR2 promotes cell cycle arrest by regulating the tumor suppressors p53-p21(CIP1), p16(INK4a), and p15(INK4b) and regulates the SASP through the induction of the acute-phase serum amyloids A1 and A2 (A-SAAs) that, in turn, function as the damage-associated molecular patterns (DAMPs) signaling through TLR2 in OIS. Last, we found evidence that the cGAS-STING cytosolic DNA sensing pathway primes TLR2 and A-SAAs expression in OIS. In summary, we report that innate immune sensing of senescence-associated DAMPs by TLR2 controls the SASP and reinforces the cell cycle arrest program in OIS. |
