Concomitant hepatocyte apoptosis and regeneration is a hallmark of chronic liver diseases (CLDs) predisposing to hepatocellular carcinoma (HCC). Here, we mechanistically link caspase-8-dependent apoptosis to HCC development via proliferation- and replication-associated DNA damage. Proliferation-associated replication stress, DNA damage, and genetic instability are detectable in CLDs before any neoplastic changes occur. Accumulated levels of hepatocyte apoptosis determine and predict subsequent hepatocarcinogenesis. Proliferation-associated DNA damage is sensed by a complex comprising caspase-8, FADD, c-FLIP, and a kinase-dependent function of RIPK1. This platform requires a non-apoptotic function of caspase-8, but no caspase-3 or caspase-8 cleavage. It may represent a DNA damage-sensing mechanism in hepatocytes that can act via JNK and subsequent phosphorylation of the histone variant H2AX.
Pharmacology, Toxicology and Pharmaceutical Science
8
3%
Other
15
6%
Unknown
84
36%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 115. 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 25 May 2022.
All research outputs
#438,637
of 31,660,612 outputs
Outputs from Cancer Cell
#239
of 3,616 outputs
Outputs of similar age
#7,242
of 341,921 outputs
Outputs of similar age from Cancer Cell
#9
of 41 outputs
Altmetric has tracked 31,660,612 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 98th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,616 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 37.9. This one has done particularly well, scoring higher than 93% of its peers.
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 341,921 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 97% of its contemporaries.
We're also able to compare this research output to 41 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 78% of its contemporaries.
