Reference : Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network.
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/139059
Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network.
English
Kuilman, Thomas [The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands > Division of Molecular Genetics > > >]
Michaloglou, Chrysiis [The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands > Division of Molecular Genetics > > >]
Vredeveld, Liesbeth C. W. [The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands > Division of Molecular Genetics > > >]
Douma, Sirith [The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands > Division of Molecular Genetics > > >]
van Doorn, Remco [Leiden University Medical Center, 2300 RC Leiden, The Netherlands > Department of Dermatology, > > >]
Desmet, Christophe mailto [Université de Liège - ULiège > Département de sciences fonctionnelles > Physiologie >]
Aarden, Lucien A. [Sanquin-AMC Landsteiner Laboratory, 1066 CX Amsterdam, The Netherlands > > > >]
Mooi, Wolter J. [VU University Medical Center, 1081 HV Amsterdam, The Netherlands > Department of Pathology > > >]
Peeper, Daniel S. [The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands > Division of Molecular Genetics > > >]
2008
Cell
133
6
1019-1031
Yes (verified by ORBi)
International
0092-8674
1097-4172
United States
[en] Adenoma/metabolism ; CCAAT-Enhancer-Binding Protein-beta/metabolism ; Cell Aging ; Cell Proliferation ; Colonic Neoplasms/metabolism ; Cyclin-Dependent Kinase Inhibitor p15/metabolism ; Cyclin-Dependent Kinase Inhibitor p16/metabolism ; Gene Expression Profiling ; Heterochromatin ; Humans ; Inflammation ; Interleukin-6/metabolism ; Interleukin-8/metabolism ; RNA Interference ; Up-Regulation
[en] Oncogene-induced cellular senescence (OIS) is emerging as a potent cancer-protective response to oncogenic events, serving to eliminate early neoplastic cells from the proliferative pool. Using combined genetic and bioinformatic analysis, we find that OIS is linked specifically to the activation of an inflammatory transcriptome. Induced genes included the pleiotropic cytokine interleukin-6 (IL-6), which upon secretion by senescent cells acted mitogenically in a paracrine fashion. Unexpectedly, IL-6 was also required for the execution of OIS, but in a cell-autonomous mode. Its depletion caused the inflammatory network to collapse and abolished senescence entry and maintenance. Furthermore, we demonstrate that the transcription factor C/EBPbeta cooperates with IL-6 to amplify the activation of the inflammatory network, including IL-8. In human colon adenomas, IL-8 specifically colocalized with arrested, p16(INK4A)-positive epithelium. We propose a model in which the context-dependent cytostatic and promitogenic functions of specific interleukins contribute to connect senescence with an inflammatory phenotype and cancer.
Researchers ; Professionals
http://hdl.handle.net/2268/139059
10.1016/j.cell.2008.03.039

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