Senescence-associated oxidative DNA damage promotes the generation of neoplastic cells.
Studies on human fibroblasts have led to viewing senescence as a barrier against tumorigenesis. Using keratinocytes, we show here that partially transformed and tumorigenic cells systematically and spontaneously emerge from senescent cultures. We show that these emerging cells are generated from senescent cells, which are still competent for replication, by an unusual budding-mitosis mechanism. We further present data implicating reactive oxygen species that accumulate during senescence as a potential mutagenic motor of this post-senescence emergence. We conclude that senescence and its associated oxidative stress could be a tumor-promoting state for epithelial cells, potentially explaining why the incidence of carcinogenesis dramatically increases with advanced age.
Gosselin
Karo
K
Université Lille Nord de France, CNRS, UMR8161, UDSL, Institut Pasteur de Lille, Lille, France.
Martien
Sébastien
S
Pourtier
Albin
A
Vercamer
Chantal
C
Ostoich
Peter
P
Morat
Luc
L
Sabatier
Laure
L
Duprez
Laurence
L
T'kint de Roodenbeke
Claire
C
Gilson
Eric
E
Malaquin
Nicolas
N
Wernert
Nicolas
N
Slijepcevic
Predrag
P
Ashtari
Marjan
M
Chelli
Fazia
F
Deruy
Emeric
E
Vandenbunder
Bernard
B
De Launoit
Yvan
Y
Abbadie
Corinne
C
D000256:Adenoviridae; D000293:Adolescent; D000328:Adult; D020087:Alu Elements; D015153:Blotting, Western; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D016922:Cellular Senescence; D020552:Comet Assay; D004249:DNA Damage; D015342:DNA Probes; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005455:Fluorescent Antibody Technique; D006801:Humans; D017403:In Situ Hybridization; D007621:Karyotyping; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D055815:Young Adult
D015342:DNA Probes; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase