@article{18b5b52e1629430f9bc1310d0d417090,
title = "The innate immune sensor Toll-like receptor 2 controls the senescence-associated secretory phenotype",
abstract = "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-p21CIP1, p16INK4a, and p15INK4b 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.",
author = "Priya Hari and Millar, {Fraser R.} and Nuria Tarrats and Jodie Birch and Andrea Quintanilla and Rink, {Curtis J.} and Irene Fern{\'a}ndez-Duran and Morwenna Muir and Finch, {Andrew J.} and Brunton, {Valerie G.} and Passos, {Jo{\~a}o F.} and Morton, {Jennifer P.} and Luke Boulter and Acosta, {Juan Carlos}",
note = "Funding Information: We especially thank M. Christophorou, A. von Kriegsheim, N. Gammoh, T. Chandra, C. Bishop, C. Wellbrock, N. Hastie, A. Jackson, M. Reijns, P. Adams, A. Banito, and all the members of J.C.A.'s laboratory for helpful criticism, discussion, and encouragement. We thank the CRUK Glasgow Centre and the BSU facilities and Histology Service at the CRUK Beatson Institute. We also thank S. W. Lowe for pT3-NRasG12V-IRES-GFP, pT3-NRasG12V/D38A-IRES-GFP, and CMV-SB13 plasmids. Publisher Copyright: {\textcopyright} 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).",
year = "2019",
month = jun,
day = "5",
doi = "10.1126/sciadv.aaw0254",
language = "English (US)",
volume = "5",
journal = "Science Advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "6",
}