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Series GSE70668 Query DataSets for GSE70668
Status Public on Aug 13, 2015
Title Mitotic stress is an integral part of the oncogene-induced senescence program that promotes multinucleation and cell cycle arrest
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Oncogene-induced senescence (OIS) is a tumor suppression mechanism that blocks cell proliferation in response to oncogenic signalling. OIS is frequently accompanied by multinucleation; however, the origin of this is unknown. Here we show that multinucleate OIS cells originated mostly from failed mitosis. Prior to senescence, mutant RasV12 activation in primary human fibroblasts compromised mitosis, associated with abnormal expression of mitotic genes that enter M-phase. Simultaneously, RasV12 activation enhanced survival of damaged mitoses, culminating in extended mitotic arrest and aberrant exit from mitosis via mitotic slippage. ERK-dependent transcriptional up-regulation of Mcl1 was responsible for enhanced slippage of cells with mitotic defects and subsequent cell survival. Importantly, mitotic slippage and oncogene signalling synergistically induced senescence and key senescence regulators p21 and p16. We propose that activated Ras induces transcriptional changes that predispose cells undergoing OIS to mitotic stress and multinucleation.
Overall design We used RNA-seq of IMR90 cells with inducible expression of oncogenic RasV12 that were synchronised in mitosis, to characterise the nature of mitotic defects that lead to multinucleation of oncogene-induced senescent cells
Contributor(s) Dikovskaya D, Cole JJ, Adams PD
Citation(s) 26299965
Submission date Jul 09, 2015
Last update date May 15, 2019
Contact name Peter Adams
Organization name University of Glasgow, Beatson Institute for Cancer Research
Street address Switchback Rd, Bearsden
City Glasgow
ZIP/Postal code G61 1BD
Country United Kingdom
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (6)
GSM1816172 DD1_ERRAS_uninduced
GSM1816173 DD2_ERRAS_uninduced
GSM1816174 DD3_ERRAS_uninduced
BioProject PRJNA289328
SRA SRP060598

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Supplementary file Size Download File type/resource
GSE70668_DD_FPKM_Matrix.csv.gz 1.2 Mb (ftp)(http) CSV
GSE70668_DD_gene_exp.diff.csv.gz 1.8 Mb (ftp)(http) CSV
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