Chemokine signaling via the CXCR2 receptor reinforces senescence
- PMID: 18555777
- DOI: 10.1016/j.cell.2008.03.038
Chemokine signaling via the CXCR2 receptor reinforces senescence
Abstract
Cells enter senescence, a state of stable proliferative arrest, in response to a variety of cellular stresses, including telomere erosion, DNA damage, and oncogenic signaling, which acts as a barrier against malignant transformation in vivo. To identify genes controlling senescence, we conducted an unbiased screen for small hairpin RNAs that extend the life span of primary human fibroblasts. Here, we report that knocking down the chemokine receptor CXCR2 (IL8RB) alleviates both replicative and oncogene-induced senescence (OIS) and diminishes the DNA-damage response. Conversely, ectopic expression of CXCR2 results in premature senescence via a p53-dependent mechanism. Cells undergoing OIS secrete multiple CXCR2-binding chemokines in a program that is regulated by the NF-kappaB and C/EBPbeta transcription factors and coordinately induce CXCR2 expression. CXCR2 upregulation is also observed in preneoplastic lesions in vivo. These results suggest that senescent cells activate a self-amplifying secretory network in which CXCR2-binding chemokines reinforce growth arrest.
Comment in
-
Unexpected pieces to the senescence puzzle.Cell. 2008 Jun 13;133(6):958-61. doi: 10.1016/j.cell.2008.05.027. Cell. 2008. PMID: 18555773 Free PMC article. Review.
Similar articles
-
Human pituitary tumor-transforming gene 1 overexpression reinforces oncogene-induced senescence through CXCR2/p21 signaling in breast cancer cells.Breast Cancer Res. 2012 Jul 12;14(4):R106. doi: 10.1186/bcr3226. Breast Cancer Res. 2012. PMID: 22789011 Free PMC article.
-
Chemokine receptor CXCR2 is transactivated by p53 and induces p38-mediated cellular senescence in response to DNA damage.Aging Cell. 2013 Dec;12(6):1110-21. doi: 10.1111/acel.12138. Epub 2013 Sep 8. Aging Cell. 2013. PMID: 23869868
-
A role for CXCR2 in senescence, but what about in cancer?Cancer Res. 2009 Mar 15;69(6):2167-70. doi: 10.1158/0008-5472.CAN-08-3772. Epub 2009 Mar 10. Cancer Res. 2009. PMID: 19276354 Review.
-
Chronic NF-kappaB activation delays RasV12-induced premature senescence of human fibroblasts by suppressing the DNA damage checkpoint response.Mech Ageing Dev. 2009 Jul;130(7):409-19. doi: 10.1016/j.mad.2009.04.002. Epub 2009 May 3. Mech Ageing Dev. 2009. PMID: 19406145 Free PMC article.
-
Control of senescence by CXCR2 and its ligands.Cell Cycle. 2008 Oct;7(19):2956-9. doi: 10.4161/cc.7.19.6780. Epub 2008 Oct 13. Cell Cycle. 2008. PMID: 18838863 Review.
Cited by
-
Novel perspectives on leptin in osteoarthritis: Focus on aging.Genes Dis. 2023 Nov 4;11(6):101159. doi: 10.1016/j.gendis.2023.101159. eCollection 2024 Nov. Genes Dis. 2023. PMID: 39229323 Free PMC article. Review.
-
Cellular senescence and SASP in tumor progression and therapeutic opportunities.Mol Cancer. 2024 Aug 31;23(1):181. doi: 10.1186/s12943-024-02096-7. Mol Cancer. 2024. PMID: 39217404 Free PMC article. Review.
-
Senescent endothelial cells: a potential target for diabetic retinopathy.Angiogenesis. 2024 Aug 31. doi: 10.1007/s10456-024-09943-7. Online ahead of print. Angiogenesis. 2024. PMID: 39215875 Review.
-
Ribosomal S6 kinase 1 regulates inflammaging via the senescence secretome.Nat Aging. 2024 Aug 29. doi: 10.1038/s43587-024-00695-z. Online ahead of print. Nat Aging. 2024. PMID: 39210150
-
Tryptanthrin targets GSTP1 to induce senescence and increases the susceptibility to apoptosis by senolytics in liver cancer cells.Redox Biol. 2024 Aug 20;76:103323. doi: 10.1016/j.redox.2024.103323. Online ahead of print. Redox Biol. 2024. PMID: 39180983 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous