Please use this identifier to cite or link to this item: https://doi.org/10.1038/emboj.2012.132
DC FieldValue
dc.titleOncogene-induced telomere dysfunction enforces cellular senescence in human cancer precursor lesions
dc.contributor.authorSuram, A
dc.contributor.authorKaplunov, J
dc.contributor.authorPatel, P.L
dc.contributor.authorRuan, H
dc.contributor.authorCerutti, A
dc.contributor.authorBoccardi, V
dc.contributor.authorFumagalli, M
dc.contributor.authorDi Micco, R
dc.contributor.authorMirani, N
dc.contributor.authorGurung, R.L
dc.contributor.authorHande, M.P
dc.contributor.authorD'Adda Di Fagagna, F
dc.contributor.authorHerbig, U
dc.date.accessioned2020-09-09T09:45:25Z
dc.date.available2020-09-09T09:45:25Z
dc.date.issued2012
dc.identifier.citationSuram, A, Kaplunov, J, Patel, P.L, Ruan, H, Cerutti, A, Boccardi, V, Fumagalli, M, Di Micco, R, Mirani, N, Gurung, R.L, Hande, M.P, D'Adda Di Fagagna, F, Herbig, U (2012). Oncogene-induced telomere dysfunction enforces cellular senescence in human cancer precursor lesions. EMBO Journal 31 (13) : 2839-2851. ScholarBank@NUS Repository. https://doi.org/10.1038/emboj.2012.132
dc.identifier.issn0261-4189
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/175333
dc.description.abstractIn normal human somatic cells, telomere dysfunction causes cellular senescence, a stable proliferative arrest with tumour suppressing properties. Whether telomere dysfunction-induced senescence (TDIS) suppresses cancer growth in humans, however, is unknown. Here, we demonstrate that multiple and distinct human cancer precursor lesions, but not corresponding malignant cancers, are comprised of cells that display hallmarks of TDIS. Furthermore, we demonstrate that oncogenic signalling, frequently associated with initiating cancer growth in humans, dramatically affected telomere structure and function by causing telomeric replication stress, rapid and stochastic telomere attrition, and consequently telomere dysfunction in cells that lack hTERT activity. DNA replication stress induced by drugs also resulted in telomere dysfunction and cellular senescence in normal human cells, demonstrating that telomeric repeats indeed are hypersensitive to DNA replication stress. Our data reveal that TDIS, accelerated by oncogene-induced DNA replication stress, is a biological response of cells in human cancer precursor lesions and provide strong evidence that TDIS is a critical tumour suppressing mechanism in humans. ©2012 European Molecular Biology Organization.
dc.sourceUnpaywall 20200831
dc.subjectbeta galactosidase
dc.subjectKi 67 antigen
dc.subjectprotein p16
dc.subjecttelomerase
dc.subjectanimal cell
dc.subjectarticle
dc.subjectcancer growth
dc.subjectcell aging
dc.subjectcell proliferation
dc.subjectchromosome structure
dc.subjectcontrolled study
dc.subjectDNA replication
dc.subjectenzyme activity
dc.subjectgene replication
dc.subjecthuman
dc.subjecthuman cell
dc.subjecthuman tissue
dc.subjectnonhuman
dc.subjectoncogene
dc.subjectpriority journal
dc.subjecttelomere
dc.subjecttelomere dysfunction induced senescence
dc.subjectCell Aging
dc.subjectCell Line
dc.subjectCell Transformation, Neoplastic
dc.subjectDNA Replication
dc.subjectHumans
dc.subjectOncogenes
dc.subjectProtein Synthesis Inhibitors
dc.subjectPuromycin
dc.subjectSignal Transduction
dc.subjectTelomere
dc.typeArticle
dc.contributor.departmentDEPT OF PHYSIOLOGY
dc.description.doi10.1038/emboj.2012.132
dc.description.sourcetitleEMBO Journal
dc.description.volume31
dc.description.issue13
dc.description.page2839-2851
dc.published.statePublished
Appears in Collections:Staff Publications
Elements

Show simple item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1038_emboj_2012_132.pdf562.59 kBAdobe PDF

OPEN

NoneView/Download

SCOPUSTM   
Citations

142
checked on Sep 19, 2021

Page view(s)

79
checked on Sep 23, 2021

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.