Please use this identifier to cite or link to this item: https://doi.org/10.1038/emboj.2012.132
Title: Oncogene-induced telomere dysfunction enforces cellular senescence in human cancer precursor lesions
Authors: Suram, 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
Keywords: beta galactosidase
Ki 67 antigen
protein p16
telomerase
animal cell
article
cancer growth
cell aging
cell proliferation
chromosome structure
controlled study
DNA replication
enzyme activity
gene replication
human
human cell
human tissue
nonhuman
oncogene
priority journal
telomere
telomere dysfunction induced senescence
Cell Aging
Cell Line
Cell Transformation, Neoplastic
DNA Replication
Humans
Oncogenes
Protein Synthesis Inhibitors
Puromycin
Signal Transduction
Telomere
Issue Date: 2012
Citation: Suram, 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
Abstract: In 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.
Source Title: EMBO Journal
URI: https://scholarbank.nus.edu.sg/handle/10635/175333
ISSN: 0261-4189
DOI: 10.1038/emboj.2012.132
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