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Attention Score in Context
| Title |
Genome-protective topoisomerase 2a-dependent G2 arrest requires p53 in hTERT-positive cancer cells
|
|---|---|
| Published in |
Cancer Research, March 2022
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| DOI | 10.1158/0008-5472.can-21-1785 |
| Pubmed ID | |
| Authors |
Nicola Lockwood, Silvia Martini, Ainara Lopez-Pardo, Katharina Deiss, Hendrika A. Segeren, Robert K. Semple, Ian Collins, Dimitra Repana, Mathias Cobbaut, Tanya Soliman, Francesca Ciccarelli, Peter J. Parker |
| Abstract |
Topoisomerase 2a (Topo2a)-dependent G2 arrest engenders faithful segregation of sister chromatids, yet in certain tumor cell lines where this arrest is dysfunctional, a PKCε-dependent failsafe pathway can be triggered. Here we elaborate on recent advances in understanding the underlying mechanisms associated with this G2 arrest by determining that p53-p21 signaling is essential for efficient arrest in cell lines, in patient-derived cells, and in colorectal cancer organoids. Regulation of this p53 axis required the SMC5/6 complex, which is distinct from the p53 pathways observed in the DNA damage response. Topo2a inhibition specifically during S phase did not trigger G2 arrest despite affecting completion of DNA replication. Moreover, in cancer cells reliant upon the alternative lengthening of telomeres (ALT) mechanism, a distinct form of Topo2a-dependent, p53-independent G2 arrest was found to be mediated by BLM and Chk1. Importantly, the previously described PKCε-dependent mitotic failsafe was engaged in hTERT-positive cells when Topo2a-dependent G2 arrest was dysfunctional and where p53 was absent, but not in cells dependent on the ALT mechanism. In PKCε knockout mice, p53 deletion elicited tumors were less aggressive than in PKCε-replete animals and exhibited a distinct pattern of chromosomal rearrangements. This evidence suggests the potential of exploiting synthetic lethality in arrest-defective hTERT-positive tumors through PKCε-directed therapeutic intervention. |
X Demographics
The data shown below were collected from the profiles of 5 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 5 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 5 | 100% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 05 August 2022.
All research outputs
#13,351,430
of 23,033,713 outputs
Outputs from Cancer Research
#13,142
of 17,954 outputs
Outputs of similar age
#183,500
of 439,473 outputs
Outputs of similar age from Cancer Research
#111
of 184 outputs
Altmetric has tracked 23,033,713 research outputs across all sources so far. This one is in the 41st percentile – i.e., 41% of other outputs scored the same or lower than it.
So far Altmetric has tracked 17,954 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.8. This one is in the 26th percentile – i.e., 26% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 439,473 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 57% of its contemporaries.
We're also able to compare this research output to 184 others from the same source and published within six weeks on either side of this one. This one is in the 38th percentile – i.e., 38% of its contemporaries scored the same or lower than it.